TUSC3 accelerates cancer growth and induces epithelial-mesenchymal transition by upregulating claudin-1 in non-small-cell lung cancer cells

Siyang Feng, Jianxue Zhai, Di Lu, Jie Lin, Xiaoying Dong, Xiguang Liu, Hua Wu, Anja C. Roden, Giovanni Brandi, Simona Tavolari, Andrea Bille, Kaican Cai

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Lung cancer is the most frequent cause of cancer-related deaths worldwide, but its molecular pathogenesis is poorly understood. The tumor suppressor candidate 3 (TUSC3) gene is located on chromosome 8p22 and is universally acknowledged as a cancer suppressor. However, our research has demonstrated that TUSC3 expression is significantly upregulated in non-small-cell lung cancer compared to benign controls. In this study, we analyzed the consequences of TUSC3 knockdown or overexpression on the biological functions of non-small-cell lung cancer cell lines. To identify the molecules and signaling pathways with which TUSC3 might interact, we completed immunoblotting, quantitative polymerase chain reaction, microarray, co-immunoprecipitation, and immunofluorescence assays. We demonstrated that TUSC3 knockdown leads to decreased proliferation, migration, and invasion, and reduced xenograft tumor growth of non-small-cell lung cancer cell lines, whereas opposite results were observed with overexpression of TUSC3. In addition, TUSC3 knockdown suppressed epithelial-mesenchymal transition by downregulating the expression of claudin-1, which plays an indispensable role in EMT progress. On the contrary, overexpression of TUSC3 significantly enhanced EMT progress by upregulating claudin-1 expression. Overall, our observations suggest that TUSC3 accelerates cancer growth and induces the epithelial-mesenchymal transition in non-small-cell lung cancer cells; we also identified claudin-1 as a target of TUSC3.

Original languageEnglish (US)
Pages (from-to)44-56
Number of pages13
JournalExperimental Cell Research
Volume373
Issue number1-2
DOIs
StatePublished - Dec 15 2018

Keywords

  • Claudin-1
  • EMT
  • Non-small-cell lung cancer
  • TUSC3

ASJC Scopus subject areas

  • Cell Biology

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