Abstract
Background
Caveolin-1 (CAV-1), the main scaffold protein in caveolae, is frequently deregulated in human cancer. Of importance, this protein has been described to show tumor suppressor or oncogenic properties depending on the cell type and the stage of the disease. In fact, its role in colorectal cancer (CRC) remains to be fully clarified due to discrepancies in the literature.
Methods
We analyzed CAV-1 by western blot in a set of early-stage CRC patients with paired tumor tissue and normal colonic mucosa available. CAV-1 mRNA and expression levels of miR-124, 133 and 802 were quantified by real-time PCR.
Results
We found CAV-1 strongly downregulated in 76.2% of tumor samples and associated with the subgroup of elderly patients (p = 0.027). We observed by real-time PCR a lack of correlation between CAV-1 mRNA and protein levels in some cases with CAV-1 downregulated by western blot, and miR-124 deregulation was identified as a potential contributing alteration to decrease CAV-1 protein expression.
Conclusion
CAV-1 is commonly downregulated in patients with primary CRC, which suggests its tumor suppressor role in early stages of this disease. Moreover, based on our findings, the previous discrepancies observed in different studies to date could be due to a complex posttranscriptional CAV-1 regulation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Nwosu ZC, Ebert MP, Dooley S et al (2016) Caveolin-1 in the regulation of cell metabolism: a cancer perspective. Mol Cancer 15:71
Liu P, Rudick M, Anderson RG (2002) Multiple functions of caveolin-1. J Biol Chem 277:41295–41298
Gupta R, Toufaily C, Annabi B (2014) Caveolin and cavin family members: dual roles in cancer. Biochimie 107:188–202
Zhang J, Zhang K, Zhou L et al (2016) Expression and potential correlation among Forkhead box protein M1, Caveolin-1 and E-cadherin in colorectal cancer. Oncol Lett 12:2381–2388
Schwencke C, Braun-Dullaeus RC, Wunderlich C et al (2006) Caveolae and caveolin in transmembrane signaling: implications for human disease. Cardiovasc Res 70:42–49
Yang SF, Yang JY, Huang CH et al (2010) Increased caveolin-1 expression associated with prolonged overall survival rate in hepatocellular carcinoma. Pathology 42:438–445
Williams TM, Lisanti MP (2005) Caveolin-1 in oncogenic transformation, cancer and metastasis. Am J Physiol Cell Physiol 288:C494–C506
Cokakli M, Erdal E, Nart D et al (2009) Differential expression of caveolin-1 in hepatocellular carcinoma: correlation with differentiation stage, motility and invasion. BMC Cancer 9:65
Fine SW, Lisanti MP, Galbiati F et al (2001) Elevated expression of caveolin-1 in adenocarcinoma of the colon. Am J Clin Pathol 115:719–724
Kim HA, Kim KH, Lee RA (2006) Expression of caveolin-1 is correlated with Akt-1 in colorectal cancer tissues. Exp Mol Pathol 80:165–170
Xue J, Wu XL, Huang XT et al (2015) Correlation of caveolin-1 expression with microlymphatic vessel density in colorectal adenocarcinoma tissues and its correlation with prognosis. Asian Pac J Trop Med 8:655–657
Bender FC, Reymond MA, Bron C et al (2000) 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 60:5870–5878
Ha TK, Her NG, Lee MG et al (2012) Caveolin-1 increases aerobic glycolysis in colorectal cancers by stimulating HMGA1-mediated GLUT3 transcription. Cancer Res 72:4097–4109
Mai J, Dosescu J, Sameni M (2005) Caveolin-1 mediates the expression and localization of cathepsin B, pro-urokinase plasminogen activator and their cell-surface receptors in human colorectal carcinoma cells. J Cell Sci 118:1493–1503
Yu F, Xie D, Ng SS et al (2015) IFITM1 promotes the metastasis of human colorectal cancer via CAV-1. Cancer Lett 368:135–143
Kitowska A, Wesserling M, Seroczynska B et al (2015) Differentiation of high-risk stage I and II colon tumors based on evaluation of CAV1 gene expression. J Surg Oncol 112:408–414
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408
Lin SY, Yeh KT, Chen WT et al (2004) Promoter CpG methylation of caveolin-1 in sporadic colorectal cancer. Anticancer Res 24:1645–1650
Dasgupta N, Kumar Thakur B, Ta A et al (2015) Caveolin-1 is transcribed from a hypermethylated promoter to mediate colonocyte differentiation and apoptosis. Exp Cell Res 334:323–336
Nohata N, Hanazawa T, Kikkawa N et al (2011) Caveolin-1 mediates tumor cell migration and invasion and its regulation by miR-133a in head and neck squamous cell carcinoma. Int J Oncol 38:209–217
Butz H, Szabó PM, Khella HW et al (2015) miRNA-target network reveals miR-124 as a key miRNA contributing to clear cell renal cell carcinoma aggressive behavior by targeting CAV1 and FLOT1. Oncotarget 6:12543–12557
Lin DH, Yue P, Pan C et al (2011) MicroRNA 802 stimulates ROMK channels by suppressing caveolin-1. J Am Soc Nephrol 22:1087–1098
Acknowledgements
This work was supported by PI15/00934 grant from “Instituto de Salud Carlos III FEDER.” B.T. is supported by “Fundación Conchita Rábago de Jiménez Díaz.”
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Torrejón, B., Cristóbal, I., Rojo, F. et al. Caveolin-1 is Markedly Downregulated in Patients with Early-Stage Colorectal Cancer. World J Surg 41, 2625–2630 (2017). https://doi.org/10.1007/s00268-017-4065-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00268-017-4065-9