Overexpression of a Novel Tumor Metastasis Suppressor Gene TMSG1/LASS2 Induces Apoptosis via a Caspase-dependent Mitochondrial Pathway.
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.
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Jing
J
Su
Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
Wenjuan
W
Yu
Department of Pathology, Peking University Shougang Hospital, Beijing, 100144, China.
Miaozi
M
Gong
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Jiangfeng
J
You
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Jianying
J
Liu
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Jie
J
Zheng
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle; D049109:Cell Proliferation; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D015398:Signal Transduction; D051049:Sphingosine N-Acyltransferase / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins; C438311:CERS2 protein, human; D051049:Sphingosine N-Acyltransferase; D020169:Caspases
APOPTOSIS; CASPASE; PROLIFERATION; TMSG1/LASS2; TUMOR METASTASIS