Dnaja3/tid1 is required for mitochondrial dna maintenance and regulates migration and invasion of human gastric cancer cells

Sheng Fan Wang, Kuo Hung Huang, Wei Chuan Tseng, Jeng Fan Lo, Anna Fen Yau Li, Wen Liang Fang, Chian Feng Chen, Tien Shun Yeh, Yuh Lih Chang, Yueh Ching Chou, Hung Hsu Hung*, Hsin Chen Lee

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish
Article number3463
Pages (from-to)1-23
Number of pages23
JournalCancers
Volume12
Issue number11
DOIs
StatePublished - Nov 2020

Keywords

  • Cancer progression
  • Galectin-7
  • Gastric cancer
  • Mitochondria
  • MMP-9
  • Tid1

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