FTO downregulation mediated by hypoxia facilitates colorectal cancer metastasis.

ABSTRACT: Fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m⁶A) demethylase, participates in tumor progression and metastasis in many malignancies, but its role in colorectal cancer (CRC) is still unclear. Here, we found that FTO protein levels, but not RNA levels, were downregulated in CRC tissues. Reduced FTO protein expression was correlated with a high recurrence rate and poor prognosis in resectable CRC patients. Moreover, we demonstrated that hypoxia restrained FTO protein expression, mainly due to an increase in ubiquitin-mediated protein degradation. The serine/threonine kinase receptor associated protein (STRAP) might served as the E3 ligase and K216 was the major ubiquitination site responsible for hypoxia-induced FTO degradation. FTO inhibited CRC metastasi

SUBMITTER: Ruan DY 

PROVIDER: S-EPMC8376648 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature