title: The motor protein KIF14 inhibits tumor growth and cancer metastasis in lung adenocarcinoma.
abstract: The motor protein kinesin superfamily proteins (KIFs) are involved in cancer progression. The depletion of one of the KIFs, KIF14, might delay the metaphase-to-anaphase transition, resulting in a binucleated status, which enhances tumor progression; however, the exact correlation between KIF14 and cancer progression remains ambiguous. In this study, using loss of heterozygosity and array comparative genomic hybridization analyses, we observed a 30% loss in the regions surrounding KIF14 on chromosome 1q in lung adenocarcinomas. In addition, the protein expression levels of KIF14 in 122 lung adenocarcinomas also indicated that approximately 30% of adenocarcinomas showed KIF14 down-regulation compared with the expression in the bronchial epithelial cells of adjacent normal counterparts. In addition, the reduced expression of KIF14 mRNA or proteins was correlated with poor overall survival (P = 0.0158 and <0.0001, respectively), and the protein levels were also inversely correlated with metastasis (P<0.0001). The overexpression of KIF14 in lung adenocarcinoma cells inhibited anchorage-independent growth in vitro and xenograft tumor growth in vivo. The overexpression and silencing of KIF14 also inhibited or enhanced cancer cell migration, invasion and adhesion to the extracellular matrix proteins laminin and collagen IV. Furthermore, we detected the adhesion molecules cadherin 11 (CDH11) and melanoma cell adhesion molecule (MCAM) as cargo on KIF14. The overexpression and silencing of KIF14 enhanced or reduced the recruitment of CDH11 in the membrane fraction, suggesting that KIF14 might act through recruiting adhesion molecules to the cell membrane and modulating cell adhesive, migratory and invasive properties. Thus, KIF14 might inhibit tumor growth and cancer metastasis in lung adenocarcinomas.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Hung
authors.forename: Tse-Ming
authors.initials: TM
authors.lastname: Hong
authors.forename: Yi-Chiung
authors.initials: YC
authors.lastname: Hsu
authors.forename: Hsuan-Yu
authors.initials: HY
authors.lastname: Chen
authors.forename: Yih-Leong
authors.initials: YL
authors.lastname: Chang
authors.forename: Chen-Tu
authors.initials: CT
authors.lastname: Wu
authors.forename: Gee-Chen
authors.initials: GC
authors.lastname: Chang
authors.forename: Yuh-Shan
authors.initials: YS
authors.lastname: Jou
authors.forename: Szu-Hua
authors.initials: SH
authors.lastname: Pan
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D051929:CD146 Antigen / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D024141:Collagen Type IV / Q000378:metabolism; D055028:Comparative Genomic Hybridization; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D051929:CD146 Antigen; D015820:Cadherins; D024141:Collagen Type IV; D007797:Laminin; C497902:MCAM protein, human; D015513:Oncogene Proteins; D034741:RNA, Small Interfering; C086960:osteoblast cadherin; C502598:KIF14 protein, human; D016547:Kinesins