MUC1 Drives the Progression and Chemoresistance of Clear Cell Renal Carcinomas.

Autor: Bourdon E; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France., Swierczewski T; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France., Goujon M; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France., Boukrout N; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France., Fellah S; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France., Van der Hauwaert C; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France., Larrue R; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France.; CHU Lille, Service de Toxicologie et Génopathies, F-59000 Lille, France., Lefebvre B; Univ. Lille, CNRS, Inserm, CHU Lille, UMR-S1172, Neuroscience & Cognition, Alzheimer & Tauopathies, F-59000 Lille, France., Van Seuningen I; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France., Cauffiez C; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France., Pottier N; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France.; Univ. Lille, CNRS, Inserm, CHU Lille, UMR-S1172, Neuroscience & Cognition, Alzheimer & Tauopathies, F-59000 Lille, France., Perrais M; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2024 Jan 17; Vol. 16 (2). Date of Electronic Publication: 2024 Jan 17.
DOI: 10.3390/cancers16020391
Abstrakt: While the transmembrane glycoprotein mucin 1 (MUC1) is clustered at the apical borders of normal epithelial cells, with transformation and loss of polarity, MUC1 is found at high levels in the cytosol and is uniformly distributed over the entire surface of carcinoma cells, where it can promote tumor progression and adversely affects the response to therapy. Clear cell renal cell carcinoma (ccRCC), the main histotype of kidney cancer, is typically highly resistant to conventional and targeted therapies for reasons that remain largely unknown. In this context, we investigated whether MUC1 also plays a pivotal role in the cellular and molecular events driving ccRCC progression and chemoresistance. We showed, using loss- and gain-of-function approaches in ccRCC-derived cell lines, that MUC1 not only influences tumor progression but also induces a multi-drug-resistant profile reminiscent of the activation of ABC drug efflux transporters. Overall, our results suggest that targeting MUC1 may represent a novel therapeutic approach to limit ccRCC progression and improve drug sensitivity.
Databáze: MEDLINE
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