Abstract
Claudins are integral structural and functional components of apical cell adhesions (tight junctions). Loss of such adhesions has been associated with malignant transformation, a process most often accompanied by a concomitant loss of claudin expression. A growing body of evidence reveals the highly contextual upregulation of claudin expression in certain cancer types, and moreover their relevance in promoting cancer cell invasion and metastatic progression. In this issue of Oncogene, Suh et al. reported on claudin-1 expression in hepatocellular carcinoma (HCC), including its role as a promoter of the epithelial−to−mesenchymal transition via the c-Abl/Raf/Ras/ERK signaling pathway. Considering the limited therapeutic options in HCC, evaluation of its role as a target merits further investigation.
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References
Roxburgh P, Evans TR . Systemic therapy of hepatocellular carcinoma: are we making progress? Adv Ther 2008; 25: 1089–1104.
Suh Y, Yoon CH, Kim RK, Lim EJ, Oh YS, Hwang SG et al. Claudin-1 induces epithelial-mesenchymal transition through activation of the c-Abl-ERK signaling pathway in human liver cells. Oncogene 2013; 32: 1743–1868.
Turksen K, Troy TC . Junctions gone bad: claudins and loss of the barrier in cancer. Biochim Biophys Acta 2011; 1816: 73–79.
Singh AB, Sharma A, Dhawan P . Claudin family of proteins and cancer: an overview. J oncol 2010; 2010: 541957.
Morin PJ . Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res 2005; 65: 9603–9606.
Myal Y, Leygue E, Blanchard AA . Claudin 1 in breast tumorigenesis: revelation of a possible novel ‘claudin high’ subset of breast cancers. J Biomed Biotechnol 2010; 2010: 956897.
Tabaries S, Dupuy F, Dong Z, Monast A, Annis MG, Spicer J et al. Claudin-2 promotes breast cancer liver metastasis by facilitating tumor cell interactions with hepatocytes. Mol Cell Biol 2012; 32: 2979–2991.
Yoon CH, Kim MJ, Park MJ, Park IC, Hwang SG, An S et al. Claudin-1 acts through c-Abl-protein kinase Cdelta (PKCdelta) signaling and has a causal role in the acquisition of invasive capacity in human liver cells. J Biol Chem 2010; 285: 226–233.
Dhawan P, Singh AB, Deane NG, No Y, Shiou SR, Schmidt C et al. Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer. J Clin Invest 2005; 115: 1765–1776.
Cervello M, McCubrey JA, Cusimano A, Lampiasi N, Azzolina A, Montalto G . Targeted therapy for hepatocellular carcinoma: novel agents on the horizon. Oncotarget 2012; 3: 236–260.
Suzuki H, Kondoh M, Takahashi A, Yagi K . Proof of concept for claudin-targeted drug development. Ann NY Acad Sci 2012; 1258: 65–70.
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JS and GG are supported by grants from Cancer Research UK, and Action against Cancer.
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Stebbing, J., Filipović, A. & Giamas, G. Claudin-1 as a promoter of EMT in hepatocellular carcinoma. Oncogene 32, 4871–4872 (2013). https://doi.org/10.1038/onc.2012.591
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DOI: https://doi.org/10.1038/onc.2012.591
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