title: LASP-1 induces proliferation, metastasis and cell cycle arrest at the G2/M phase in gallbladder cancer by down-regulating S100P via the PI3K/AKT pathway.
abstract: LASP-1 is an actin-binding protein that regulates cytoskeletal dynamics and cell migration. LASP-1 was previously identified in a cDNA library from metastatic breast cancer samples. This protein has since been detected in multiple human cancers, including liver cancer, gastric cancer and pancreatic cancer. S100P is a small calcium-binding protein in the S100 protein family that regulates cellular, physiological and pathological processes in various cancers. However, the clinical significance of LASP-1 and S100P expression in gallbladder cancer (GBC) is not yet clear. In our study, we focused on the clinical significance, biological function and mechanism of LASP-1 in gallbladder cancer and detected LASP-1 and S100P overexpression in GBC tissues. The expression of LASP-1 was significantly correlated with poor prognosis in GBC patients (P < 0.05). Furthermore, down-regulation of LASP-1 expression resulted in the obvious inhibition of proliferation and migration and caused cell cycle arrest by down-regulating S100P via the PI3K/AKT pathway; in mice, tumor volume was significantly decreased. In conclusion, LASP-1 may act as an oncogene to regulate the expression of S100P to influence cellular functions in GBC. LASP-1 could serve as a genetic treatment target in GBC patients.
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: ZhiZhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: YuanYuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: XuAn
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: HongChen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Yijian
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: YaoHui
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Mingzhe
authors.initials: M
authors.lastname: Weng
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: HaiBin
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: MaoLan
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Shibo
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Runfa
authors.initials: R
authors.lastname: Bao
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Xiyong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhen
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China. Electronic address: dongqian71@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China. Electronic address: liuybphd@126.com.
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints; D005706:Gallbladder Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D000067492:RNAi Therapeutics; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins; C096353:LASP1 protein, human; D060588:LIM Domain Proteins; D009363:Neoplasm Proteins; C103003:S100P protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: Cell cycle; Gallbladder cancer; LASP-1; Metastasis; Proliferation; S100P