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DNAJA3/Tid1 Is Required for Mitochondrial DNA Maintenance and Regulates Migration and Invasion of Human Gastric Cancer Cells.


ABSTRACT:

Background

Gastric cancer is a common health issue. Deregulated cellular energetics is regarded as a cancer hallmark and mitochondrial dysfunction might contribute to cancer progression. Tid1, a mitochondrial co-chaperone, may play a role as a tumor suppressor in various cancers, but the role of Tid1 in gastric cancers remains under investigated.

Methods

The clinical TCGA online database and immunohistochemical staining for Tid1 expression in tumor samples of gastric cancer patients were analyzed. Tid1 knockdown by siRNA was applied to investigate the role of Tid1 in gastric cancer cells.

Results

Low Tid1 protein-expressing gastric cancer patients had a poorer prognosis and higher lymph node invasion than high Tid1-expressing patients. Knockdown of Tid1 did not increase cell proliferation, colony/tumor sphere formation, or chemotherapy resistance in gastric cancer cells. However, Tid1 knockdown increased cell migration and invasion. Moreover, Tid1 knockdown reduced the mtDNA copy number of gastric cancer cells. In addition, the Tid1-galectin-7-MMP-9 axis might be associated with Tid1 knockdown-induced cell migration and invasion of gastric cancer cells.

Conclusions

Tid1 is required for mtDNA maintenance and regulates migration and invasion of gastric cancer cells. Tid1 deletion may be a poor prognostic factor in gastric cancers and could be further investigated for development of gastric cancer treatments.

SUBMITTER: Wang SF 

PROVIDER: S-EPMC7699785 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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DNAJA3/Tid1 Is Required for Mitochondrial DNA Maintenance and Regulates Migration and Invasion of Human Gastric Cancer Cells.

Wang Sheng-Fan SF   Huang Kuo-Hung KH   Tseng Wei-Chuan WC   Lo Jeng-Fan JF   Li Anna Fen-Yau AF   Fang Wen-Liang WL   Chen Chian-Feng CF   Yeh Tien-Shun TS   Chang Yuh-Lih YL   Chou Yueh-Ching YC   Hung Hung-Hsu HH   Lee Hsin-Chen HC  

Cancers 20201120 11


<h4>Background</h4>Gastric cancer is a common health issue. Deregulated cellular energetics is regarded as a cancer hallmark and mitochondrial dysfunction might contribute to cancer progression. Tid1, a mitochondrial co-chaperone, may play a role as a tumor suppressor in various cancers, but the role of Tid1 in gastric cancers remains under investigated.<h4>Methods</h4>The clinical TCGA online database and immunohistochemical staining for Tid1 expression in tumor samples of gastric cancer patien  ...[more]

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