Isoprenylcysteine carboxylmethyltransferase is required for the impact of mutant KRAS on TAZ protein level and cancer cell self-renewal.

ABSTRACT: Cancer stem cells possess the capacity for self-renewal and resistance to chemotherapy. It is therefore crucial to understand the molecular regulators of stemness in the quest to develop effective cancer therapies. TAZ is a transcription activator that promotes stem cell functions in post-development mammalian cells; suppression of TAZ activity reduces or eliminates cancer stemness in select cancers. Isoprenylcysteine carboxylmethyltransferase (ICMT) is the unique enzyme of the last step of posttranslational prenylation processing pathway that modifies several oncogenic proteins, including RAS. We found that suppression of ICMT results in reduced self-renewal/stemness in KRAS-driven pancreatic and breast cancer cells. Silencing of ICMT led to significant reduction of TAZ protein levels and

SUBMITTER: Chai TF 

PROVIDER: S-EPMC7391290 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature