Format

Send to

Choose Destination
Exp Cell Res. 2018 Dec 15;373(1-2):44-56. doi: 10.1016/j.yexcr.2018.08.012. Epub 2018 Aug 9.

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

Author information

1
Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
2
Department of Pathology, Nanfang Hospital & School of Basic Medicine, Southern Medical University, 1838 Guangzhou Avenue, Guangzhou 510515, PR China.
3
Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, USA.
4
Department of Experimental, Diagnostic and Specialty Medicine, University Hospital S. Orsola, Malpighi Bologna, via Massarenti 9, 40138, Italy.
5
Department of Thoracic Surgery, Guy's Hospital, London, UK.
6
Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China. Electronic address: doc_cai@163.com.

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.

KEYWORDS:

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

PMID:
30098333
DOI:
10.1016/j.yexcr.2018.08.012
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center