PDE2 Inhibits PKA-Mediated Phosphorylation of TFAM to Promote Mitochondrial Ca²⁺-Induced Colorectal Cancer Growth.

ABSTRACT: Growing evidence indicates that the dysregulation of mitochondrial calcium (Ca²⁺) plays a critical role in the growth of tumor cells, including colorectal cancer (CRC). However, the underling mechanism is not fully elucidated. In this study, the regulatory effects of mitochondrial Ca²⁺ on phosphodiesterase 2 (PDE2)/cAMP/PKA axis and the phosphorylation of mitochondrial transcription factor A (TFAM) as well as the growth of CRC cells were systematically investigated both in vitro and in vivo. Our findings demonstrated that MCU-induced mitochondrial Ca²⁺ uptake activated mitochondrial PDE2 in CRC cells. Moreover, overexpression MCU in CRC led to a 1.9-fold increase in Ca²⁺ uptake compared to control cells. However, knockdown of MCU re

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC8256694 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature