Caspase-8 expression and its Src-dependent phosphorylation on Tyr380 promote cancer cell neoplastic transformation and resistance to anoikis

Giulia Fianco, Caterina Cenci, D Barilà

Research output: Contribution to journalArticle

Abstract

Caspase-8 expression is lost in a small percentage of tumors suggesting that the retention of its functionality may positively contribute to tumor progression. Consistently, several non-apoptotic functions of Caspase-8 have been identified and Caspase-8 has been shown to modulate cell adhesion, migration and to promote tumor progression. We have previously identified the Src-dependent phosphorylation of Caspase-8 on Tyr380 as a molecular mechanism to downregulate the proapoptotic function of Caspase-8; this phosphorylation occurs in colon cancer and may promote cell migration in neuroblastoma cell lines. However, the occurrence of Caspase-8 phosphorylation on Tyr380 and its significance in different carcinoma cellular models, have not been clarified yet. Here we show that Caspase-8 expression may promote cell transformation in glioblastoma and in hepatocarcinoma cell lines. In these systems Caspase-8 is phosphorylated on Tyr380 in a Src kinase dependent manner and this phosphorylation is required for transformation and it is enhanced by hypoxic conditions. Using a cancer cellular model characterized by Src constitutive activation engineered to express either Caspase-8-wt or Caspase-8-Y380F we could show that Caspase-8 expression and its phosphorylation on Tyr380, but not its enzymatic activity, promote in vitro cell transformation and resistance to anoikis. This work demonstrates a dual role for Caspase-8 in cancer, suggesting that Tyr380 phosphorylation may represent a molecular switch to hijack its activity from tumor suppressor to tumor promoter.

Original languageEnglish
Pages (from-to)114-22
Number of pages9
JournalExperimental Cell Research
Volume347
Issue number1
DOIs
Publication statusPublished - Sep 10 2016

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Neoplastic Cell Transformation
Anoikis
Caspase 8
Phosphorylation
Neoplasms
Cell Movement
Cell Line
src-Family Kinases
Glioblastoma
Neuroblastoma
Cell Adhesion
Carcinogens
Colonic Neoplasms

Keywords

  • Journal Article

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Caspase-8 expression and its Src-dependent phosphorylation on Tyr380 promote cancer cell neoplastic transformation and resistance to anoikis. / Fianco, Giulia; Cenci, Caterina; Barilà, D.

In: Experimental Cell Research, Vol. 347, No. 1, 10.09.2016, p. 114-22.

Research output: Contribution to journalArticle

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AU - Barilà, D

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