Cylindromatosis is required for survival of a subset of melanoma cells.

Cylindromatosis is required for survival of a subset of melanoma cells. Oncol Res. 2020 Apr 06;: Authors: La T, Jin L, Liu XY, Song ZH, Farrelly M, Feng YC, Yan XG, Zhang YY, Thorne RF, Zhang XD, Teng L Abstract The deubiquitinase cyclindromatosis (CYLD) functions as a tumour suppressor inhibiting cell proliferation in many cancer types including melanoma. Here we present evidence that a proportion of melanoma cells are nonetheless addicted to CYLD for survival. The expression levels of CYLD varied widely in melanoma cell lines and melanomas in vivo, with a subset of melanoma cell lines and melanomas displaying even higher levels of CYLD than melanocyte lines and nevi, respectively. Strikingly, although shRNA knockdown of CYLD promoted, as anticipated, cell proliferation in some melanoma cell lines, it reduced cell viability in a fraction of melanoma cell lines with relatively high levels of CYLD expression and did not impinge on survival and proliferation in a third type of melanoma cell lines. The decrease in cell viability caused by CYLD knockdown was due to induction of apoptosis, as it was associated with activation of the caspase cascade and was abolished by treatment with a general caspase inhibitor. Mechanistic investigation s demonstrated that induction of apoptosis by CYLD knockdown was caused by upregulation of receptor-interacting protein kinase 1 (RIPK1) that was associated with elevated K63-linked polyubiquitination of ...
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research