title: Reduced Expression of Galectin-9 Contributes to a Poor Outcome in Colon Cancer by Inhibiting NK Cell Chemotaxis Partially through the Rho/ROCK1 Signaling Pathway.
abstract: Galectin-9 is a widely expressed protein that is involved in immune regulation and tumorpathogenesis and serves as a marker of a poor prognosis in various types of cancers. However, the clinical impact and the precise mechanism by which this protein contributes to colon tumor progression are unclear. In the present study, we detected the expression of galectin-9 and CD56 cells using immunohistochemistry. Spearman's rank correlation was used to clarify the association between galectin-9 expression and natural killer (NK) cell infiltration. The influence of galectin-9 on NK-92 cell migration was evaluated in vitro using transwell chemotaxis assays. The role of rh-galectin-9 in F-actin polarization in NK-92 cells was investigated using laser scanning confocal microscopy. We showed that galectin-9 was expressed in 101 (78.91%) colon tumor tissues and that was expressed at lower levels in these tissues than in para-tumor tissues. Low levels of galectin-9 expression were positively correlated with a poor histological grade and lymph node metastasis (P<0.05). A Kaplan-Meier method and Cox proportional hazards regression analysis showed that overall survival was longer in patients with high galectin-9 expression in an 8-year follow-up (P<0.05). Spearman's rank correlation indicated that there was a linear correlation between galectin-9 expression and CD56+ NK cell infiltration (R(2) = 0.658; P<0.0001). Galectin-9 stimulated migration in human NK-92 cells by affecting F-actin polarization through the Rho/ROCK1 signaling pathway. These results suggest that galectin-9 expression potentially represents a novel mechanism for tumors to escape immune surveillance in colon tumors.
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Jintang
authors.initials: J
authors.lastname: Sun
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Gao
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Bingfeng
authors.initials: B
authors.lastname: Song
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xue
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Shao
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Chemotherapy, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Huayang
authors.initials: H
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Meixiang
authors.initials: M
authors.lastname: Yang
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Xun
authors.initials: X
authors.lastname: Qu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002633:Chemotaxis; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D037161:Galectins / Q000096:biosynthesis* / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000276:immunology; D015398:Signal Transduction; D015996:Survival Rate; D019139:Tumor Escape; D054460:rho-Associated Kinases / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D037161:Galectins; C105032:LGALS9 protein, human; D009363:Neoplasm Proteins; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases