UFM1 Suppresses Invasive Activities of Gastric Cancer Cells by Attenuating the Expres7sion of PDK1 Through PI3K/AKT Signaling

Overview

Journal J Exp Clin Cancer Res

Publisher Biomed Central

Specialty Oncology

Date 2019 Sep 20

PMID 31533855

Citations 38

Authors

Jian-Xian Lin

Xin-Sheng Xie

Xiong-Feng Weng

Sheng-Liang Qiu

Changhwan Yoon

Ning-Zi Lian

Jian-Wei Xie

Jia-Bin Wang

Jun Lu

Qi-Yue Chen

Long-Long Cao

Mi Lin

Ru-Hong Tu

Ying-hong Yang

Chang-Ming Huang

Chao-Hui Zheng

Ping Li

Affiliations

Soon will be listed here.

Abstract

Background: UFM1 has been found to be involved in the regulation of tumor development. This study aims to clarify the role and potential molecular mechanisms of UFM1 in the invasion and metastasis of gastric cancer.

Methods: Expression of UFM1 in gastric tumor and paired adjacent noncancerous tissues from 437 patients was analyzed by Western blotting, immunohistochemistry, and realtime PCR. Its correlation with the clinicopathological characteristics and prognosis of gastric cancer patients was analyzed. The effects of UFM1 on the invasion and migration of gastric cancer cells were determined by the wound and trans-well assays, and the effect of UFM1 on subcutaneous tumor formation was verified in nude mice. The potential downstream targets of UFM1 and related molecular mechanisms were clarified by the human protein kinase assay and co-immunoprecipitation technique.

Results: Compared with the corresponding adjacent tissues, the transcription level and protein expression level of UFM1 in gastric cancer tissues were significantly downregulated (P < 0.05). The 5-year survival rate of gastric cancer patients with low UFM1 expression was significantly lower than the patients with high UFM1 expression (42.1% vs 63.0%, P < 0.05). The invasion and migration abilities of gastric cancer cells with stable UFM1 overexpression were significantly decreased, and the gastric cancer cells with UFM1 stable knockdown showed the opposite results; similar results were also obtained in the nude mouse model. Further studies have revealed that UFM1 could increase the ubiquitination level of PDK1 and decrease the expression of PDK1 at protein level, thereby inhibiting the phosphorylation level of AKT at Ser473. Additionally, the effect of UFM1 on gastric cancer cell function is dependent on the expression of PDK1. The expression level of UFM1 can improve the poor prognosis of PDK1 in patients with gastric cancer.

Conclusion: UFM1 suppresses the invasion and metastasis of gastric cancer by increasing the ubiquitination of PDK1 through negatively regulating PI3K/AKT signaling.

Citing Articles

Role of UFMylation in tumorigenesis and cancer immunotherapy.

Ding L, Jiang X, Li T, Wang S Front Immunol. 2024; 15:1454823.

PMID: 39247188 PMC: 11377280. DOI: 10.3389/fimmu.2024.1454823.

UFM1 inhibits hypoxia-induced angiogenesis via promoting proteasome degradation of HIF-1α.

Jing Y, Ye K, Zhang G, Zhu J, Mao Z, Zhang Q Mol Cell Biochem. 2024; 479(7):1833-1852.

PMID: 38722467 DOI: 10.1007/s11010-024-05013-0.

Quantitative proteome and lysine succinylome characterization of zinc chloride smoke-induced lung injury in mice.

Zhou R, Tu Z, Chen D, Wang W, Liu S, She L Heliyon. 2024; 10(6):e27450.

PMID: 38524532 PMC: 10957386. DOI: 10.1016/j.heliyon.2024.e27450.

LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior.

Liu X, Zhang W, Meng N, Lin L, Tang G Open Life Sci. 2024; 19(1):20220806.

PMID: 38283117 PMC: 10811526. DOI: 10.1515/biol-2022-0806.

Correction: UFM1 suppresses invasive activities of gastric cancer cells by attenuating the expression of PDK1 through PI3K/AKT signaling.

Lin J, Xie X, Weng X, Qiu S, Yoon C, Lian N J Exp Clin Cancer Res. 2023; 42(1):307.

PMID: 37990274 PMC: 10662863. DOI: 10.1186/s13046-023-02896-7.

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