TCRP1 Activated by Mutant P53 Promotes NSCLC Proliferation Via Inhibiting FOXO3a

Overview

Journal Oncogenesis

Date 2022 Apr 23

PMID 35459265

Authors

Hao Liu

Xiaoting Jia

Kai Luo

Xiangzhou Chen

Zhijie Zhang

Danyang Chen

Yixue Gu

Zhimin He

Guopei Zheng

Affiliations

Soon will be listed here.

Abstract

Previously, our lab explored that tongue cancer resistance-associated protein (TCRP1) plays a central role in cancer chemo-resistance and progression. Absolutely, TCRP1 was significantly increased in lung cancer. But the mechanism is far from elucidated. Here, we found that TCRP1 was increased in p53-mutant non-small-cell lung cancer (NSCLC), comparing to that in NSCLC with wild type p53. Further study showed that mutant p53 couldn't bind to the promoter of TCRP1 to inhibit its expression. While the wild type p53 did so. Next, loss-and gain-of-function assays demonstrated that TCRP1 promoted cell proliferation and tumor growth in NSCLC. Regarding the mechanism, TCRP1 encouraged AKT phosphorylation and blocked FOXO3a nuclear localization through favoring FOXO3a ubiquitination in cytoplasm, thus, promoted cell cycle progression. Conclusionly, TCRP1 was upregulated in NSCLC cells with mutant p53. TCRP1 promoted NSCLC progression via regulating cell cycle.

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