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Overexpression of a Novel Tumor Metastasis Suppressor Gene TMSG1/LASS2 Induces Apoptosis via a Caspase‐dependent Mitochondrial Pathway
Author(s) -
Su Jing,
Yu Wenjuan,
Gong Miaozi,
You Jiangfeng,
Liu Jianying,
Zheng Jie
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25086
Subject(s) - biology , cell growth , cell cycle , apoptosis , microbiology and biotechnology , transfection , metastasis suppressor , cancer research , cell cycle checkpoint , propidium iodide , cell culture , programmed cell death , gene , suppressor , genetics
The tumor metastasis suppressor gene 1 (TMSG1), also designated homo sapiens longevity assurance homologue 2 of yeast LAG1 (LASS2), is a novel tumor metastatic suppressor gene. Although its effects on metastasis have been reported, its biological functions remain unclear. The purpose of this study was to investigate the effects of TMSG1/LASS2 protein on apoptosis and proliferation in human embryonic kidney cell lines HEK293 and 293 T and explore the potential mechanisms. Cell growth, morphology, expressions of apoptotic‐related proteins and cell cycle distribution were evaluated in HEK293 and 293 T cells transfected with TMSG1/LASS2 expression plasmids or vector controls. MTT assays showed that overexpression of TMSG1/LASS2 inhibited cell proliferation; and morphological observations and flow cytometric assays with Annexin V/propidium iodide showed TMSG1/LASS2 overexpression increased apoptosis in these cells. Western blot analysis demonstrated that overexpression of TMSG1/LASS2 resulted in the downregulation of Bcl‐2, release of cytochrome c from mitochondria, activation of procaspase‐9 and procaspase‐3, and the cleavage of PARP. Subsequent cell cycle analysis showed that TMSG1/LASS2 overexpression inhibited cell proliferation by mediating the induction of G0/G1 cell cycle arrest. Together, these results confirmed that TMSG1/LASS2 is a potential metastasis suppressor gene, and suggested that the mechanism involved the induction of apoptosis and inhibition of cell proliferation via a caspase‐dependent mitochondrial pathway. J. Cell. Biochem. 116: 1310–1317, 2015. © 2015 Wiley Periodicals, Inc.