Silencing of LASS2/TMSG1 enhances invasion and metastasis capacity of prostate cancer cell.
Homo sapiens longevity assurance homolog 2 of yeast LAG1 (LASS2), also known as tumor metastasis suppressor gene 1 (TMSG1), was firstly cloned by our laboratory in 1999. However, its antitumor molecular mechanisms are still unclear. LASS2/TMSG-1 could directly interact with the C subunit of Vacuolar H(+) ATPase (V-ATPase), which suggested that LASS2/TMSG1 might inhibit the invasion and metastasis through regulating the function of V-ATPase. In this study, we explored the effect of small hairpin RNA (shRNA) targeting LASS2/TMSG1 on the invasion and metastasis of human prostate carcinoma cell line PC-3M-2B4 with low metastatic potential and its functional interaction with V-ATPase. Silencing of LASS2/TMSG1 gene in PC-3M-2B4 cells increased V-ATPase activity, extracellular hydrogen ion concentration and in turn the activation of secreted MMP-2 and MMP-9, which coincided with enhancing cell proliferation, cell survival, and cell invasion in vitro, as well as acceleration of prostate cancer (PCA) growth and lymph node metastases in vivo. Thus we concluded that silencing of LASS2/TMSG1 enhances invasion and metastasis of PCA cell through increase of V-ATPase activity. These results establish LASS2/TMSG1 as a promising therapeutic target for advanced PCA.
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, P.R. China; Department of Pathology, School of Basic Medical Sciences, Inner Monglia Medical College, Huhhot, 010059, P.R. China; Department of Pathology, The Affiliated Hospital of Inner Monglia Medical College, Huhhot, 010059, P.R. China.
Xiaoyan
X
Xu
Beiying
B
Liu
Pengcheng
P
Zou
Yan
Y
Zhang
Jiangfeng
J
You
Fei
F
Pei
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D020868:Gene Silencing; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D051049:Sphingosine N-Acyltransferase / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D008565:Membrane Proteins; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; C438311:CERS2 protein, human; D051049:Sphingosine N-Acyltransferase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D025262:Vacuolar Proton-Translocating ATPases
LASS2/TMSG1; PC-3M-2B4 CELLS; PROSTATE CARCINOMA; VACUOLAR H+ ATPase; shRNA