title: Loss of large tumor suppressor 1 promotes growth and metastasis of gastric cancer cells through upregulation of the YAP signaling.
abstract: Accumulating evidence shows that large tumor suppressor 1 (LATS1) as a novel resident governor of cellular homeostasis is implicated in multiple tumorigenic properties including cell growth, apoptosis and metastasis. However, the contribution of LATS1 to gastric carcinoma (GC) remains unclear. The correlation of LATS1 expression with clinicopathologic characteristics, GC prognosis and recurrence was analyzed by immunohistochemistry, Univariate and Kaplan-Meier analysis. Functional experiments were performed to investigate biological behaviors of GC cells and underlying molecular mechanisms. Tumor growth and metastasis was assessed in vivo using orthotopic implantation GC models in severe combined immune deficiency (SCID) mice. Consequently, decreased LATS1 expression was significantly associated with the lymph node metastasis, poor prognosis and recurrence. Ectopic expression of LATS1 decreased GC cell proliferation and invasion in vitro and inhibited tumor growth and liver metastasis in vivo, but depletion of LATS1 expression restored the invasive phenotype. Further observation indicated that YAP pathway was required for LATS1-induced inhibition of cell growth and invasion, and LATS1 restrained nuclear transfer of YAP, downregulated YAP, PCNA, CTGF, MMP-2, MMP-9, Bcl-2 and CyclinD1 expression and upregulated p-YAP and Bax expression. Our findings suggest that LATS1 is a potential candidate tumor suppressor and inhibits the growth and metastasis of GC cells via downregulation of the YAP signaling.
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Gerontology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Chu
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Jin-Shui
authors.initials: JS
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Li-Qiong
authors.initials: LQ
authors.lastname: Xia
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Yun-Min
authors.initials: YM
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Da
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Sun
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism*; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D014157:Transcription Factors; D015854:Up-Regulation; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C092745:LATS1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: YAP; gastric cancer; large tumor suppressor 1; metastasis; prognosis