Disruption of the cell-cell junction with concomitant changes in the expression of junctional proteins is a hallmark of cancer cell invasion and metastasis. The role of adherent junction proteins has been studied extensively in cancer, but the roles of tight junction (TJ) proteins are less well understood. Claudins are recently identified members of the tetraspanin family of proteins, which are integral to the structure and function of TJs. Recent studies show changes in expression/cellular localization of claudins during tumorigenesis; however, a causal relationship between claudin expression/localization and cancer has not been established. Here, we report an increased expression of claudin-1 in human primary colon carcinoma and metastasis and in cell lines derived from primary and metastatic tumors. We also report frequent nuclear localization of claudin-1 in these samples. Genetic manipulations of claudin-1 expression in colon cancer cell lines induced changes in cellular phenotype, with structural and functional changes in markers of epithelial-mesenchymal transition. Furthermore, we demonstrate that changes in claudin-1 expression have significant effects on growth of xenografted tumors and metastasis in athymic mice. We further provide data suggesting that the regulation of E-cadherin expression and β-catenin/Tcf signaling is a possible mechanism underlying claudin-1–dependent changes.
Punita Dhawan, Amar B. Singh, Natasha G. Deane, YiRan No, Sheng-Ru Shiou, Carl Schmidt, John Neff, M. Kay Washington, R. Daniel Beauchamp
Title and authors | Publication | Year |
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Improving the response to oxaliplatin by targeting chemotherapy-induced CLDN1 in resistant metastatic colorectal cancer cells
Sara Cherradi, Véronique Garambois, Johanna Marines, Augusto Augusto Faria Andrade1,, Alexandra Fauvre, Olivia Morand, Manon Fargal, Ferial Mancouri, Adeline Ayrolles-Torro, Nadia Vezzo-Vié, MARTA Jarlier, Gérald Lossaint, Steve Huvelle, Nicolas Joubert, Thibault Mazard, Céline Gongora, Philippe Pourquier, Florence Boissière, Maguy DEL RIO |
Cell & Bioscience | 2023 |
LIN28B promotes cell invasion and colorectal cancer metastasis via the induction of CLDN1 and NOTCH3
Yasunori Masuike, Kensuke Sugiura, Kensuke Suzuki, Alice E Shin, Nozomu Sakai, Hisahiro Matsubara, Masayuki Otsuka, Peter Sims, Christopher Lengner, Anil Rustgi |
JCI Insight | 2023 |
Tight Junction Protein Signaling and Cancer Biology.
Nehme Z, Roehlen N, Dhawan P, Baumert TF |
Cells | 2023 |
P62/SQSTM1 binds with claudin-2 to target for selective autophagy in stressed intestinal epithelium
Ahmad R, Kumar B, Tamang RL, Talmon GA, Dhawan P, Singh AB |
Communications biology | 2023 |
Pyrroline-5-Carboxylate Reductase-2 Promotes Colorectal Carcinogenesis by Modulating Microtubule-Associated Serine/Threonine Kinase-like/Wnt/β-Catenin Signaling
Lama Tamang R, Kumar B, Patel SM, Thapa I, Ahmad A, Kumar V, Ahmad R, Becker DF, Bastola D(, Dhawan P, Singh AB |
Cells | 2023 |
cCPE Fusion Proteins as Molecular Probes to Detect Claudins and Tight Junction Dysregulation in Gastrointestinal Cell Lines, Tissue Explants and Patient-Derived Organoids
Waldow A, Beier LS, Arndt J, Schallenberg S, Vollbrecht C, Bischoff P, Farrera-Sal M, Loch FN, Bojarski C, Schumann M, Winkler L, Kamphues C, Ehlen L, Piontek J |
Pharmaceutics | 2023 |
Expression of Claudins in Preneoplastic Conditions of the Gastrointestinal Tract: A Review.
Ouban A, Arabi TZ |
Cancers | 2023 |
Aberrant Expression of Claudins in Head and Neck Carcinomas and Their Prognostic and Therapeutic Value: A Narrative Review
Arabi TZ, Algheryafi LA, Alodah NA, Enabi HM, Alshehry AA, Ouban A |
Cancers | 2023 |
Discovery, synthesis and biological evaluation of a series of N-(phenylcarbamothioyl)-2-napthamides as inhibitors of Claudin-1
Mashinson V, Webster TM, Vadukoot AK, Tolentino KT, Simeon P, Fatima I, Dhawan P, Hopkins CR |
Bioorganic & Medicinal Chemistry | 2023 |
Expression patterns of claudins in cancer
Tao D, Guan B, Li H, Zhou C |
Heliyon | 2023 |
Tight Junction Claudins and Occludin Are Differentially Regulated and Expressed in Genomically Defined Subsets of Colon Cancer
Voutsadakis IA |
Current issues in molecular biology | 2023 |
Claudin-1 interacts with EPHA2 to promote cancer stemness and chemoresistance in colorectal cancer.
Primeaux M, Liu X, Gowrikumar S, Fatima I, Fisher KW, Bastola D, Vecchio AJ, Singh AB, Dhawan P |
Cancer Letters | 2023 |
Identification and characterization of a first-generation inhibitor of claudin-1 in Colon Cancer progression and metastasis
Fatima I, Uppada JP, Chhonker YS, Gowrikumar S, Barman S, Roy S, Tolentino KT, Palermo N, Natarajan A, Beauchamp DR, Vecchio A, Murry DJ, Singh AB, Hopkins CR, Dhawan P |
Biomedicine & Pharmacotherapy | 2023 |