Home LiteratureArticle Details
PMID: 25801618 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Caveolae and signalling in cancer.

Nature reviews. Cancer ·Vol. 15 ·No. 4 ·2015-04-00 ·Pages 225-37

Martinez-Outschoorn UE, Sotgia F, Lisanti MP

Abstract

It has been over 20 years since the discovery that caveolar lipid rafts function as signalling organelles. Lipid rafts create plasma membrane heterogeneity, and caveolae are the most extensively studied subset of lipid rafts. A newly emerging paradigm is that changes in caveolae also generate tumour metabolic heterogeneity. Altered caveolae create a catabolic tumour microenvironment, which supports oxidative mitochondrial metabolism in cancer cells and which contributes to dismal survival rates for cancer patients. In this Review, we discuss the role of caveolae in tumour progression, with a special emphasis on their metabolic and cell signalling effects, and their capacity to transform the tumour microenvironment.

MeSH Terms
Animals Caveolae/metabolism Humans Membrane Microdomains Neoplasms/metabolism,pathology Signal Transduction
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Martinez-Outschoorn Ubaldo E
Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Sotgia Federica
1] Breakthrough Breast Cancer Research Unit, Institute of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK. [2] Manchester Centre for Cellular Metabolism (MCCM), University of Manchester, Manchester M20 4BX, UK.
Lisanti Michael P
1] Breakthrough Breast Cancer Research Unit, Institute of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK. [2] Manchester Centre for Cellular Metabolism (MCCM), University of Manchester, Manchester M20 4BX, UK.
References (182)
182 references, click to expand
  1. A local paracrine and endocrine network involving TGFβ, Cox-2, ROS, and estrogen receptor β influences reactive stromal cell regulation of prostate cancer cell motility.
    Mol Endocrinol. 2012 Jun;26(6):940-54 PMID: 22593181
  2. Silibinin prevents prostate cancer cell-mediated differentiation of naïve fibroblasts into cancer-associated fibroblast phenotype by targeting TGF β2.
    Mol Carcinog. 2015 Sep;54(9):730-41 PMID: 24615813
  3. CD36 is palmitoylated on both N- and C-terminal cytoplasmic tails.
    J Biol Chem. 1996 Sep 13;271(37):22315-20 PMID: 8798390
  4. Antitumor effects of in vivo caveolin gene delivery are associated with the inhibition of the proangiogenic and vasodilatory effects of nitric oxide.
    FASEB J. 2005 Apr;19(6):602-4 PMID: 15623570
  5. Evidence for a stromal-epithelial "lactate shuttle" in human tumors: MCT4 is a marker of oxidative stress in cancer-associated fibroblasts.
    Cell Cycle. 2011 Jun 1;10(11):1772-83 PMID: 21558814
  6. Cancer associated fibroblasts express pro-inflammatory factors in human breast and ovarian tumors.
    Biochem Biophys Res Commun. 2013 Aug 2;437(3):397-402 PMID: 23831470
  7. Synergy in tumor suppression by direct interaction of neutral endopeptidase with PTEN.
    Cancer Cell. 2004 Jan;5(1):67-78 PMID: 14749127
  8. Oxidative stress promotes myofibroblast differentiation and tumour spreading.
    EMBO Mol Med. 2010 Jun;2(6):211-30 PMID: 20535745
  9. Perturbational profiling of a cell-line model of tumorigenesis by using metabolic measurements.
    Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):5992-7 PMID: 15840712
  10. Cross-species functional analysis of cancer-associated fibroblasts identifies a critical role for CLCF1 and IL-6 in non-small cell lung cancer in vivo.
    Cancer Res. 2012 Nov 15;72(22):5744-56 PMID: 22962265
  11. Loss of stromal caveolin-1 expression in malignant melanoma metastases predicts poor survival.
    Cell Cycle. 2011 Dec 15;10(24):4250-5 PMID: 22134245
  12. Congenital generalized lipodystrophy, type 4 (CGL4) associated with myopathy due to novel PTRF mutations.
    Am J Med Genet A. 2010 Sep;152A(9):2245-53 PMID: 20684003
  13. The dually acylated NH2-terminal domain of gi1alpha is sufficient to target a green fluorescent protein reporter to caveolin-enriched plasma membrane domains. Palmitoylation of caveolin-1 is required for the recognition of dually acylated g-protein alpha subunits in vivo.
    J Biol Chem. 1999 Feb 26;274(9):5843-50 PMID: 10026207
  14. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization.
    Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10625-9 PMID: 7938003
  15. Immunopurification and characterization of rat adipocyte caveolae suggest their dissociation from insulin signaling.
    J Biol Chem. 2003 May 16;278(20):18321-9 PMID: 12637562
  16. Caveolins, a family of scaffolding proteins for organizing "preassembled signaling complexes" at the plasma membrane.
    J Biol Chem. 1998 Mar 6;273(10):5419-22 PMID: 9488658
  17. The multiple faces of caveolae.
    Nat Rev Mol Cell Biol. 2007 Mar;8(3):185-94 PMID: 17318224
  18. Hyperactivation of oxidative mitochondrial metabolism in epithelial cancer cells in situ: visualizing the therapeutic effects of metformin in tumor tissue.
    Cell Cycle. 2011 Dec 1;10(23):4047-64 PMID: 22134189
  19. Tumor cell growth inhibition by caveolin re-expression in human breast cancer cells.
    Oncogene. 1998 Mar;16(11):1391-7 PMID: 9525738
  20. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors.
    Cell. 2005 Feb 25;120(4):513-22 PMID: 15734683
  21. Expression of the candidate tumor suppressor gene hSRBC is frequently lost in primary lung cancers with and without DNA methylation.
    Oncogene. 2005 Sep 15;24(41):6249-55 PMID: 15940253
  22. Reduction of caveolin and caveolae in oncogenically transformed cells.
    Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1381-5 PMID: 7877987
  23. Caveolin-1 expression negatively regulates cell cycle progression by inducing G(0)/G(1) arrest via a p53/p21(WAF1/Cip1)-dependent mechanism.
    Mol Biol Cell. 2001 Aug;12(8):2229-44 PMID: 11514613
  24. Pyruvate kinase expression (PKM1 and PKM2) in cancer-associated fibroblasts drives stromal nutrient production and tumor growth.
    Cancer Biol Ther. 2011 Dec 15;12(12):1101-13 PMID: 22236875
  25. Progression from ductal carcinoma in situ to invasive breast cancer: revisited.
    Mol Oncol. 2013 Oct;7(5):859-69 PMID: 23890733
  26. Loss of caveolin-1 and gain of MCT4 expression in the tumor stroma: key events in the progression from an in situ to an invasive breast carcinoma.
    Cell Cycle. 2013 Aug 15;12(16):2684-90 PMID: 23907124
  27. Cancer-associated fibroblasts promote proliferation of endometrial cancer cells.
    PLoS One. 2013 Jul 26;8(7):e68923 PMID: 23922669
  28. Caveolin-1-/- null mammary stromal fibroblasts share characteristics with human breast cancer-associated fibroblasts.
    Am J Pathol. 2009 Mar;174(3):746-61 PMID: 19234134
  29. Down-regulation of stromal caveolin-1 expression in esophageal squamous cell carcinoma: a potent predictor of lymph node metastases, early tumor recurrence, and poor prognosis.
    Ann Surg Oncol. 2014 Jan;21(1):329-36 PMID: 23982252
  30. The fluid mosaic model of the structure of cell membranes.
    Science. 1972 Feb 18;175(4023):720-31 PMID: 4333397
  31. HIF1-alpha functions as a tumor promoter in cancer associated fibroblasts, and as a tumor suppressor in breast cancer cells: Autophagy drives compartment-specific oncogenesis.
    Cell Cycle. 2010 Sep 1;9(17):3534-51 PMID: 20864819
  32. Metabolic alterations in lung cancer-associated fibroblasts correlated with increased glycolytic metabolism of the tumor.
    Mol Cancer Res. 2013 Jun;11(6):579-92 PMID: 23475953
  33. Absence of caveolin-1 sensitizes mouse skin to carcinogen-induced epidermal hyperplasia and tumor formation.
    Am J Pathol. 2003 Jun;162(6):2029-39 PMID: 12759258
  34. A 60-kDa protein abundant in adipocyte caveolae.
    Cell Tissue Res. 2001 Jul;305(1):99-106 PMID: 11512676
  35. Redox-induced Src kinase and caveolin-1 signaling in TGF-β1-initiated SMAD2/3 activation and PAI-1 expression.
    PLoS One. 2011;6(7):e22896 PMID: 21829547
  36. Replicative senescence in normal liver, chronic hepatitis C, and hepatocellular carcinomas.
    Hum Pathol. 2001 Mar;32(3):327-32 PMID: 11274643
  37. Clinical and functional significance of loss of caveolin-1 expression in breast cancer-associated fibroblasts.
    J Pathol. 2012 Aug;227(4):490-8 PMID: 22488553
  38. Caveolin mRNA levels are up-regulated by free cholesterol and down-regulated by oxysterols in fibroblast monolayers.
    Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3753-8 PMID: 9108050
  39. Elevated expression of TGF-beta1 in head and neck cancer-associated fibroblasts.
    Mol Carcinog. 2004 Jun;40(2):116-21 PMID: 15170816
  40. Caveolae, caveolin and cav-p60 in smooth muscle and renin-producing cells in the rat kidney.
    Acta Physiol Scand. 2003 Oct;179(2):179-88 PMID: 14510782
  41. An absence of stromal caveolin-1 is associated with advanced prostate cancer, metastatic disease and epithelial Akt activation.
    Cell Cycle. 2009 Aug;8(15):2420-4 PMID: 19556867
  42. The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms.
    Cancer Res. 2006 Jan 15;66(2):794-802 PMID: 16424011
  43. Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities.
    J Biol Chem. 1997 Nov 28;272(48):30429-38 PMID: 9374534
  44. Deficiency of caveolin-1 in Apc(min/+) mice promotes colorectal tumorigenesis.
    Carcinogenesis. 2013 Sep;34(9):2109-18 PMID: 23640045
  45. Pathologic caveolin-1 regulation of PTEN in idiopathic pulmonary fibrosis.
    Am J Pathol. 2010 Jun;176(6):2626-37 PMID: 20395445
  46. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth.
    Nat Med. 2011 Oct 30;17(11):1498-503 PMID: 22037646
  47. Src tyrosine kinases, Galpha subunits, and H-Ras share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the auto-activation of Src tyrosine kinases.
    J Biol Chem. 1996 Nov 15;271(46):29182-90 PMID: 8910575
  48. Pretreatment mitochondrial priming correlates with clinical response to cytotoxic chemotherapy.
    Science. 2011 Nov 25;334(6059):1129-33 PMID: 22033517
  49. The chemokine growth-regulated oncogene 1 (Gro-1) links RAS signaling to the senescence of stromal fibroblasts and ovarian tumorigenesis.
    Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16472-7 PMID: 17060621
  50. Caveolin-1 and mitochondrial SOD2 (MnSOD) function as tumor suppressors in the stromal microenvironment: a new genetically tractable model for human cancer associated fibroblasts.
    Cancer Biol Ther. 2011 Feb 15;11(4):383-94 PMID: 21150282
  51. Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments.
    Nat Commun. 2014;5:3295 PMID: 24548894
  52. PTRF/cavin-1 neutralizes non-caveolar caveolin-1 microdomains in prostate cancer.
    Oncogene. 2014 Jul 3;33(27):3561-70 PMID: 23934189
  53. The lipoatrophic caveolin-1 deficient mouse model reveals autophagy in mature adipocytes.
    Autophagy. 2010 Aug;6(6):754-63 PMID: 20574167
  54. Targeting of nitric oxide synthase to endothelial cell caveolae via palmitoylation: implications for nitric oxide signaling.
    Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6448-53 PMID: 8692835
  55. Caveolin-1 mutations (P132L and null) and the pathogenesis of breast cancer: caveolin-1 (P132L) behaves in a dominant-negative manner and caveolin-1 (-/-) null mice show mammary epithelial cell hyperplasia.
    Am J Pathol. 2002 Oct;161(4):1357-69 PMID: 12368209
  56. Nitric oxide-mediated inhibition of the mitochondrial respiratory chain in cultured astrocytes.
    J Neurochem. 1994 Sep;63(3):910-6 PMID: 7519665
  57. Direct interaction of endothelial nitric-oxide synthase and caveolin-1 inhibits synthase activity.
    J Biol Chem. 1997 Jul 25;272(30):18522-5 PMID: 9228013
  58. Structure and function of sphingolipid- and cholesterol-rich membrane rafts.
    J Biol Chem. 2000 Jun 9;275(23):17221-4 PMID: 10770957
  59. Stromal cell expression of caveolin-1 predicts outcome in breast cancer.
    Am J Pathol. 2009 Jun;174(6):2035-43 PMID: 19411449
  60. Fatal cardiac arrhythmia and long-QT syndrome in a new form of congenital generalized lipodystrophy with muscle rippling (CGL4) due to PTRF-CAVIN mutations.
    PLoS Genet. 2010 Mar 12;6(3):e1000874 PMID: 20300641
  61. p42/44 MAP kinase-dependent and -independent signaling pathways regulate caveolin-1 gene expression. Activation of Ras-MAP kinase and protein kinase a signaling cascades transcriptionally down-regulates caveolin-1 promoter activity.
    J Biol Chem. 1999 Nov 5;274(45):32333-41 PMID: 10542274
  62. Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner.
    Cancer Cell. 2010 Feb 17;17(2):135-47 PMID: 20138012
  63. S-nitrosation of mitochondrial complex I depends on its structural conformation.
    J Biol Chem. 2007 Dec 28;282(52):37448-53 PMID: 17956863
  64. The reggie/flotillin connection to growth.
    Trends Cell Biol. 2010 Jan;20(1):6-13 PMID: 19896850
  65. Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging.
    Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12072-7 PMID: 11593017
  66. Using the "reverse Warburg effect" to identify high-risk breast cancer patients: stromal MCT4 predicts poor clinical outcome in triple-negative breast cancers.
    Cell Cycle. 2012 Mar 15;11(6):1108-17 PMID: 22313602
  67. Oligomeric structure of caveolin: implications for caveolae membrane organization.
    Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9407-11 PMID: 7568142
  68. Palmitoylation of caveolin-1 at a single site (Cys-156) controls its coupling to the c-Src tyrosine kinase: targeting of dually acylated molecules (GPI-linked, transmembrane, or cytoplasmic) to caveolae effectively uncouples c-Src and caveolin-1 (TYR-14).
    J Biol Chem. 2001 Sep 14;276(37):35150-8 PMID: 11451957
  69. Caveolin-1, a metastasis-related gene that promotes cell survival in prostate cancer.
    Apoptosis. 1999 Aug;4(4):233-7 PMID: 14634273
  70. Cholesterol depletion of caveolae causes hyperactivation of extracellular signal-related kinase (ERK).
    J Biol Chem. 1998 Aug 14;273(33):21099-104 PMID: 9694863
  71. Caveolin-1 promotes autoregulatory, Akt-mediated induction of cancer-promoting growth factors in prostate cancer cells.
    Mol Cancer Res. 2009 Nov;7(11):1781-91 PMID: 19903767
  72. Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface.
    Cell. 1992 Feb 7;68(3):533-44 PMID: 1531449
  73. Pacsin 2 is recruited to caveolae and functions in caveolar biogenesis.
    J Cell Sci. 2011 Aug 15;124(Pt 16):2777-85 PMID: 21807942
  74. Architectural and mechanistic insights into an EHD ATPase involved in membrane remodelling.
    Nature. 2007 Oct 18;449(7164):923-7 PMID: 17914359
  75. Sphingomyelinase induces lipid microdomain formation in a fluid phosphatidylcholine/sphingomyelin membrane.
    Biochemistry. 1998 Dec 15;37(50):17562-70 PMID: 9860872
  76. The metabolic interactions between tumor cells and tumor-associated stroma (TAS) in prostatic cancer.
    Cancer Biol Ther. 2012 Nov;13(13):1284-9 PMID: 22895074
  77. Caveolin-1 is a critical determinant of autophagy, metabolic switching, and oxidative stress in vascular endothelium.
    PLoS One. 2014 Feb 03;9(2):e87871 PMID: 24498385
  78. Caveolin-I overexpression is a favourable prognostic factor for patients with extrahepatic bile duct carcinoma.
    Br J Cancer. 2003 Apr 22;88(8):1234-8 PMID: 12737162
  79. Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor.
    J Biol Chem. 2001 Mar 2;276(9):6727-38 PMID: 11102446
  80. Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis.
    Cell. 2011 Jul 8;146(1):148-63 PMID: 21729786
  81. Stabilization of caveolin-1 by cellular cholesterol and scavenger receptor class B type I.
    Biochemistry. 2002 Oct 1;41(39):11931-40 PMID: 12269838
  82. Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides.
    Nature. 2014 Apr 3;508(7494):108-12 PMID: 24670634
  83. Reciprocal metabolic reprogramming through lactate shuttle coordinately influences tumor-stroma interplay.
    Cancer Res. 2012 Oct 1;72(19):5130-40 PMID: 22850421
  84. Rafts defined: a report on the Keystone Symposium on Lipid Rafts and Cell Function.
    J Lipid Res. 2006 Jul;47(7):1597-8 PMID: 16645198
  85. The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1alpha-dependent mechanism.
    J Biol Chem. 2006 Apr 7;281(14):9030-7 PMID: 16452478
  86. Pten in stromal fibroblasts suppresses mammary epithelial tumours.
    Nature. 2009 Oct 22;461(7267):1084-91 PMID: 19847259
  87. Caveolin-1 deficiency causes cholesterol-dependent mitochondrial dysfunction and apoptotic susceptibility.
    Curr Biol. 2011 Apr 26;21(8):681-6 PMID: 21497090
  88. Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts.
    Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):20009-14 PMID: 21041659
  89. Hypercholesterolemia decreases nitric oxide production by promoting the interaction of caveolin and endothelial nitric oxide synthase.
    J Clin Invest. 1999 Mar;103(6):897-905 PMID: 10079111
  90. The cyclin D1 gene is transcriptionally repressed by caveolin-1.
    J Biol Chem. 2000 Jul 14;275(28):21203-9 PMID: 10747899
  91. Co-purification and direct interaction of Ras with caveolin, an integral membrane protein of caveolae microdomains. Detergent-free purification of caveolae microdomains.
    J Biol Chem. 1996 Apr 19;271(16):9690-7 PMID: 8621645
  92. The shape of caveolae is omega-like after glutaraldehyde fixation and cup-like after cryofixation.
    Histochem Cell Biol. 2010 Feb;133(2):223-8 PMID: 19851779
  93. Tumor-stroma metabolic relationship based on lactate shuttle can sustain prostate cancer progression.
    BMC Cancer. 2014 Mar 05;14:154 PMID: 24597899
  94. VIP21/caveolin is a cholesterol-binding protein.
    Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10339-43 PMID: 7479780
  95. Caveolin-1 gene disruption promotes mammary tumorigenesis and dramatically enhances lung metastasis in vivo. Role of Cav-1 in cell invasiveness and matrix metalloproteinase (MMP-2/9) secretion.
    J Biol Chem. 2004 Dec 3;279(49):51630-46 PMID: 15355971
  96. Transforming growth factor-β1 (TGF-β1)-stimulated fibroblast to myofibroblast differentiation is mediated by hyaluronan (HA)-facilitated epidermal growth factor receptor (EGFR) and CD44 co-localization in lipid rafts.
    J Biol Chem. 2013 May 24;288(21):14824-38 PMID: 23589287
  97. Ketone bodies and two-compartment tumor metabolism: stromal ketone production fuels mitochondrial biogenesis in epithelial cancer cells.
    Cell Cycle. 2012 Nov 1;11(21):3956-63 PMID: 23082721
  98. Caveolin-1 tumor-promoting role in human melanoma.
    Int J Cancer. 2009 Oct 1;125(7):1514-22 PMID: 19521982
  99. Targeted downregulation of caveolin-1 is sufficient to drive cell transformation and hyperactivate the p42/44 MAP kinase cascade.
    EMBO J. 1998 Nov 16;17(22):6633-48 PMID: 9822607
  100. Caveolin-1 levels are down-regulated in human colon tumors, and ectopic expression of caveolin-1 in colon carcinoma cell lines reduces cell tumorigenicity.
    Cancer Res. 2000 Oct 15;60(20):5870-8 PMID: 11059785
  101. Does nitric oxide modulate mitochondrial energy generation and apoptosis?
    Nat Rev Mol Cell Biol. 2002 Mar;3(3):214-20 PMID: 11994742
  102. Invasion activating caveolin-1 mutation in human scirrhous breast cancers.
    Cancer Res. 2001 Mar 15;61(6):2361-4 PMID: 11289096
  103. Nitric oxide inhibits mitochondrial NADH:ubiquinone reductase activity through peroxynitrite formation.
    Biochem J. 2001 Oct 1;359(Pt 1):139-45 PMID: 11563977
  104. TGF-beta in CAF-mediated tumor growth and metastasis.
    Semin Cancer Biol. 2014 Apr;25:15-22 PMID: 24412104
  105. Functional rafts in cell membranes.
    Nature. 1997 Jun 5;387(6633):569-72 PMID: 9177342
  106. MURC/Cavin-4 and cavin family members form tissue-specific caveolar complexes.
    J Cell Biol. 2009 Jun 29;185(7):1259-73 PMID: 19546242
  107. The fine structure of the gall bladder epithelium of the mouse.
    J Biophys Biochem Cytol. 1955 Sep 25;1(5):445-58 PMID: 13263332
  108. Identification of peptide and protein ligands for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolae-associated proteins.
    J Biol Chem. 1997 Mar 7;272(10):6525-33 PMID: 9045678
  109. CD36 repression activates a multicellular stromal program shared by high mammographic density and tumor tissues.
    Cancer Discov. 2012 Sep;2(9):826-39 PMID: 22777768
  110. Cholesterol-rich lipid rafts mediate akt-regulated survival in prostate cancer cells.
    Cancer Res. 2002 Apr 15;62(8):2227-31 PMID: 11956073
  111. Distinct dedifferentiation processes affect caveolin-1 expression in hepatocytes.
    Cell Commun Signal. 2013 Jan 22;11(1):6 PMID: 23339737
  112. Deletion of cavin genes reveals tissue-specific mechanisms for morphogenesis of endothelial caveolae.
    Nat Commun. 2013;4:1831 PMID: 23652019
  113. Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis.
    Genes Dev. 2000 Jan 15;14(2):163-76 PMID: 10652271
  114. Caveolin-1 and cancer metabolism in the tumor microenvironment: markers, models, and mechanisms.
    Annu Rev Pathol. 2012;7:423-67 PMID: 22077552
  115. Autophagy in cancer associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NFκB activation in the tumor stromal microenvironment.
    Cell Cycle. 2010 Sep 1;9(17):3515-33 PMID: 20855962
  116. Non-existence of caveolin-1 gene mutations in human breast cancer.
    Breast Cancer Res Treat. 2012 Jan;131(1):307-10 PMID: 21909981
  117. Caveolin-1 expression in clinically confined human prostate cancer: a novel prognostic marker.
    Cancer Res. 1999 Nov 15;59(22):5719-23 PMID: 10582690
  118. Cancer-associated fibroblasts expressing CXCL14 rely upon NOS1-derived nitric oxide signaling for their tumor-supporting properties.
    Cancer Res. 2014 Jun 1;74(11):2999-3010 PMID: 24710408
  119. Caveolae regulate the nanoscale organization of the plasma membrane to remotely control Ras signaling.
    J Cell Biol. 2014 Mar 3;204(5):777-92 PMID: 24567358
  120. An absence of stromal caveolin-1 expression predicts early tumor recurrence and poor clinical outcome in human breast cancers.
    Am J Pathol. 2009 Jun;174(6):2023-34 PMID: 19411448
  121. Caveolin-1 null (-/-) mice show dramatic reductions in life span.
    Biochemistry. 2003 Dec 30;42(51):15124-31 PMID: 14690422
  122. Caveolin-1 and accelerated host aging in the breast tumor microenvironment: chemoprevention with rapamycin, an mTOR inhibitor and anti-aging drug.
    Am J Pathol. 2012 Jul;181(1):278-93 PMID: 22698676
  123. Caveolin-1 up-regulation during epithelial to mesenchymal transition is mediated by focal adhesion kinase.
    J Biol Chem. 2008 May 16;283(20):13714-24 PMID: 18332144
  124. Caveolae as plasma membrane sensors, protectors and organizers.
    Nat Rev Mol Cell Biol. 2013 Feb;14(2):98-112 PMID: 23340574
  125. Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-κB/IL-8 pathway that drives tumor angiogenesis.
    Cancer Res. 2011 Apr 1;71(7):2550-60 PMID: 21300765
  126. Caveolin-1 and regulation of cellular cholesterol homeostasis.
    Am J Physiol Heart Circ Physiol. 2006 Aug;291(2):H677-86 PMID: 16603689
  127. Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice.
    Science. 2001 Sep 28;293(5539):2449-52 PMID: 11498544
  128. The lipid raft hypothesis revisited--new insights on raft composition and function from super-resolution fluorescence microscopy.
    Bioessays. 2012 Sep;34(9):739-47 PMID: 22696155
  129. Cytokine production and inflammation drive autophagy in the tumor microenvironment: role of stromal caveolin-1 as a key regulator.
    Cell Cycle. 2011 Jun 1;10 (11):1784-93 PMID: 21566463
  130. Metabolic reprogramming of cancer-associated fibroblasts by TGF-β drives tumor growth: connecting TGF-β signaling with "Warburg-like" cancer metabolism and L-lactate production.
    Cell Cycle. 2012 Aug 15;11(16):3019-35 PMID: 22874531
  131. Redistribution of caveolae during mitosis.
    J Cell Sci. 2011 Jun 15;124(Pt 12):1965-72 PMID: 21625007
  132. Breast cancer cells induce stromal fibroblasts to express MMP-9 via secretion of TNF-alpha and TGF-beta.
    J Cell Sci. 2005 May 15;118(Pt 10):2143-53 PMID: 15855236
  133. Regulation of raft-dependent endocytosis.
    J Cell Mol Med. 2007 Jul-Aug;11(4):644-53 PMID: 17760830
  134. PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function.
    Cell. 2008 Jan 11;132(1):113-24 PMID: 18191225
  135. Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities.
    J Biol Chem. 2001 Oct 12;276(41):38121-38 PMID: 11457855
  136. Endothelial nitric oxide synthase is regulated by tyrosine phosphorylation and interacts with caveolin-1.
    J Biol Chem. 1996 Nov 1;271(44):27237-40 PMID: 8910295
  137. Essential role of PACSIN2/syndapin-II in caveolae membrane sculpting.
    J Cell Sci. 2011 Jun 15;124(Pt 12):2032-40 PMID: 21610094
  138. Understanding the Warburg effect and the prognostic value of stromal caveolin-1 as a marker of a lethal tumor microenvironment.
    Breast Cancer Res. 2011 Jul 08;13(4):213 PMID: 21867571
  139. Caveolin-3 associates with developing T-tubules during muscle differentiation.
    J Cell Biol. 1997 Jan 13;136(1):137-54 PMID: 9008709
  140. Oxidative stress inhibits caveolin-1 palmitoylation and trafficking in endothelial cells.
    Biochem J. 2002 Feb 1;361(Pt 3):681-8 PMID: 11802799
  141. Caveolin-1 (P132L), a common breast cancer mutation, confers mammary cell invasiveness and defines a novel stem cell/metastasis-associated gene signature.
    Am J Pathol. 2009 May;174(5):1650-62 PMID: 19395651
  142. Caveolin-1 expression level in cancer associated fibroblasts predicts outcome in gastric cancer.
    PLoS One. 2013;8(3):e59102 PMID: 23527097
  143. Impact of tumor microenvironment and epithelial phenotypes on metabolism in breast cancer.
    Clin Cancer Res. 2013 Feb 1;19(3):571-85 PMID: 23236214
  144. Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B.
    Nat Med. 2012 Sep;18(9):1359-68 PMID: 22863786
  145. EHD2 regulates caveolar dynamics via ATP-driven targeting and oligomerization.
    Mol Biol Cell. 2012 Apr;23(7):1316-29 PMID: 22323287
  146. Organization in lipid membranes containing cholesterol.
    Phys Rev Lett. 2002 Dec 23;89(26):268101 PMID: 12484857
  147. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha.
    Nature. 2008 Jun 5;453(7196):807-11 PMID: 18432192
  148. Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis.
    Science. 2004 Jul 2;305(5680):99-103 PMID: 15232110
  149. Metabolic phenotypes in primary unknown metastatic carcinoma.
    J Transl Med. 2014 Jan 06;12:2 PMID: 24387319
  150. Down-regulation of the cavin family proteins in breast cancer.
    J Cell Biochem. 2012 Jan;113(1):322-8 PMID: 21913217
  151. De novo formation of caveolae in lymphocytes by expression of VIP21-caveolin.
    Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8655-9 PMID: 7567992
  152. Caveolin-1-deficient mice have increased tumor microvascular permeability, angiogenesis, and growth.
    Cancer Res. 2007 Mar 15;67(6):2849-56 PMID: 17363608
  153. Nitric oxide induces coupling of mitochondrial signalling with the endoplasmic reticulum stress response.
    Nat Cell Biol. 2004 Nov;6(11):1129-34 PMID: 15502820
  154. Value of caveolin-1 in cancer progression and prognosis: Emphasis on cancer-associated fibroblasts, human cancer cells and mechanism of caveolin-1 expression (Review).
    Oncol Lett. 2014 Oct;8(4):1409-1421 PMID: 25202343
  155. The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells.
    Biochem J. 2000 Aug 15;350 Pt 1:219-27 PMID: 10926847
  156. Regulated internalization of caveolae.
    J Cell Biol. 1994 Dec;127(5):1199-215 PMID: 7962085
  157. Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice.
    Nat Genet. 1998 Mar;18(3):231-6 PMID: 9500544
  158. Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional significance of the nos caveolin binding domain in vivo.
    J Biol Chem. 1997 Oct 10;272(41):25437-40 PMID: 9325253
  159. Caveolin, a protein component of caveolae membrane coats.
    Cell. 1992 Feb 21;68(4):673-82 PMID: 1739974
  160. Genetic ablation of Cav1 differentially affects melanoma tumor growth and metastasis in mice: role of Cav1 in Shh heterotypic signaling and transendothelial migration.
    Cancer Res. 2012 May 1;72(9):2262-74 PMID: 22396494
  161. Lipid rafts as a membrane-organizing principle.
    Science. 2010 Jan 1;327(5961):46-50 PMID: 20044567
  162. Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization.
    Nat Cell Biol. 2005 Sep;7(9):901-8 PMID: 16113676
  163. Catabolic cancer-associated fibroblasts transfer energy and biomass to anabolic cancer cells, fueling tumor growth.
    Semin Cancer Biol. 2014 Apr;25:47-60 PMID: 24486645
  164. Phosphorylated caveolin-1 regulates Rho/ROCK-dependent focal adhesion dynamics and tumor cell migration and invasion.
    Cancer Res. 2008 Oct 15;68(20):8210-20 PMID: 18922892
  165. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis.
    Cell. 2006 Jul 14;126(1):121-34 PMID: 16839881
  166. Altered mitochondrial function and metabolic inflexibility associated with loss of caveolin-1.
    Cell Metab. 2012 Feb 8;15(2):171-85 PMID: 22326219
  167. Mitochondria and cancer.
    Nat Rev Cancer. 2012 Oct;12(10):685-98 PMID: 23001348
  168. Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene.
    Am J Pathol. 2001 Nov;159(5):1635-43 PMID: 11696424
  169. Differential caveolin-1 polarization in endothelial cells during migration in two and three dimensions.
    Mol Biol Cell. 2003 Aug;14(8):3156-68 PMID: 12925753
  170. Opposing effects of reactive oxygen species and cholesterol on endothelial nitric oxide synthase and endothelial cell caveolae.
    Circ Res. 1999 Jul 9;85(1):29-37 PMID: 10400908
  171. Divergent control of Cav-1 expression in non-cancerous Li-Fraumeni syndrome and human cancer cell lines.
    Cancer Biol Ther. 2013 Jan;14(1):29-38 PMID: 23114650
  172. High-resolution mapping reveals topologically distinct cellular pools of phosphatidylserine.
    J Cell Biol. 2011 Jul 25;194(2):257-75 PMID: 21788369
  173. The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma.
    Cell Cycle. 2009 Dec;8(23):3984-4001 PMID: 19923890
  174. Caveolae, caveolin and caveolin-rich membrane domains: a signalling hypothesis.
    Trends Cell Biol. 1994 Jul;4(7):231-5 PMID: 14731661
  175. Acylation targets emdothelial nitric-oxide synthase to plasmalemmal caveolae.
    J Biol Chem. 1996 Mar 15;271(11):6518-22 PMID: 8626455
  176. Different roles for caveolin-1 in the development of non-small cell lung cancer versus small cell lung cancer.
    Cancer Res. 2004 Jun 15;64(12):4277-85 PMID: 15205342
  177. Ketones and lactate "fuel" tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism.
    Cell Cycle. 2010 Sep 1;9(17):3506-14 PMID: 20818174
  178. Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation.
    Cancer Cell. 2012 Nov 13;22(5):571-84 PMID: 23153532
  179. Restoration of caveolin-1 expression suppresses growth and metastasis of head and neck squamous cell carcinoma.
    Br J Cancer. 2008 Nov 18;99(10):1684-94 PMID: 19002186
  180. Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: a morphologic, ultrastructural, immunohistochemical, and in situ hybridization analysis.
    Clin Cancer Res. 2007 Jan 1;13(1):90-101 PMID: 17200343
  181. Caveolin is palmitoylated on multiple cysteine residues. Palmitoylation is not necessary for localization of caveolin to caveolae.
    J Biol Chem. 1995 Mar 24;270(12):6838-42 PMID: 7896831
  182. Loss of caveolin-1 in prostate cancer stroma correlates with reduced relapse-free survival and is functionally relevant to tumour progression.
    J Pathol. 2013 Sep;231(1):77-87 PMID: 23729330
Article Info
Journal
Nature reviews. Cancer
Abbr.
Nat Rev Cancer
ISSN
1474-1768
DOI
10.1038/nrc3915
Published
2015-04-00
Pages
225-37
Language
English
Region
England
NLM ID
101124168
Subset
IM
Grants
NCI NIH HHS · K08 CA175193‑01A1 · United States
External Links
PubMed source DOI: 10.1038/nrc3915 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2