Abstract:
: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.
journal_name
Proteomicsjournal_title
Proteomicsauthors
Sidahmed-Adrar N,Ottavi JF,Benzoubir N,Ait Saadi T,Bou Saleh M,Mauduit P,Guettier C,Desterke C,Le Naour Fdoi
10.1002/pmic.201900025subject
Has Abstractpub_date
2019-11-01 00:00:00pages
e1900025issue
21-22eissn
1615-9853issn
1615-9861journal_volume
19pub_type
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