Tspan15 Is a New Stemness-Related Marker in Hepatocellular Carcinoma.

Autor: Sidahmed-Adrar N; Inserm, Unité 1193, Villejuif, F-94800, France.; Université Paris-Sud, Institut André Lwoff, Villejuif, F-94800, France., Ottavi JF; Inserm, Unité 1193, Villejuif, F-94800, France.; Université Paris-Sud, Institut André Lwoff, Villejuif, F-94800, France., Benzoubir N; Inserm, Unité 1193, Villejuif, F-94800, France.; Université Paris-Sud, Institut André Lwoff, Villejuif, F-94800, France., Ait Saadi T; Inserm, Unité 1193, Villejuif, F-94800, France.; Université Paris-Sud, Institut André Lwoff, Villejuif, F-94800, France., Bou Saleh M; Inserm, Unité 1193, Villejuif, F-94800, France.; Université Paris-Sud, Institut André Lwoff, Villejuif, F-94800, France., Mauduit P; Université Paris-Sud, Institut André Lwoff, Villejuif, F-94800, France.; Inserm, Unité 1197, Villejuif, F-94800, France., Guettier C; Inserm, Unité 1193, Villejuif, F-94800, France.; Université Paris-Sud, Institut André Lwoff, Villejuif, F-94800, France.; AP-HP Hôpital Bicêtre, Service d'Anatomopathologie, Le Kremlin-Bicêtre, F-94275, France., Desterke C; Université Paris-Sud, Institut André Lwoff, Villejuif, F-94800, France.; Inserm, US33, Villejuif, F-94800, France., Le Naour F; Inserm, Unité 1193, Villejuif, F-94800, France.; Université Paris-Sud, Institut André Lwoff, Villejuif, F-94800, France.; Inserm, US33, Villejuif, F-94800, France.
Jazyk: angličtina
Zdroj: Proteomics [Proteomics] 2019 Nov; Vol. 19 (21-22), pp. e1900025. Date of Electronic Publication: 2019 Sep 02.
DOI: 10.1002/pmic.201900025
Abstrakt: Hepatocellular carcinoma (HCC) is the second cause of cancer-related deaths worldwide. A clearer understanding of the molecular mechanisms underlying tumor growth and invasiveness remains crucial for developing new therapies. Here, the expression of tetraspanins, a family of plasma membrane organizers involved in tumor progression, has been addressed. Integrative approaches combining transcriptomics and bioinformatics allow demonstrating the induced and heterogeneous expression of Tspan15 in HCC. Tspan15 positive tumors exhibit signatures related to hepatic progenitor cells as well as recurrence of cancer. Immunohistochemistry experiments confirm Tspan15 expression in the subset of HCC expressing stemness-related markers such as EpCAM and Cytokeratin-19. Functional networks reveal that most of these genes expressed in correlation to Tspan15 support cell proliferation. Furthermore, Tspan15 overexpression in the hepatoma cell line HepG2 significantly increases cell proliferation. A quantitative proteomic analysis of the secretome reveals a higher abundance of the protein connective tissue growth factor (CTGF), a pleiotropic matricellular signaling protein. Proteomic profiling of Tspan15 complexes allows identifying numerous membrane proteins including several growth factor receptors. Finally, Tspan15 increases ERK1/2 phosphorylation that directly controls CTGF expression and secretion. In conclusion, Tspan15 is a new stemness-related marker in HCC which exhibits high potential of tumor growth and recurrence.
(© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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