title: Opposite role of Kindlin-1 and Kindlin-2 in lung cancers.
abstract: Lung cancer is highly heterogenous and is composed of various subtypes that are in diverse differential stages. The newly identified integrin-interacting proteins Kindlin-1 and Kindlin-2 are the activators of transmembrane receptor integrins that play important roles in cancer progression. In this report we present the expression profiles of Kindlin-1 and Kindlin-2 in lung cancers using patient specimens and established their correlation with lung cancer progression. We found that Kindlin-1 was expressed in epithelia-derived non-small-cell lung cancer, especially in squamous cell lung cancer but expressed at low levels in poorly differentiated large cell lung cancer. However, Kindlin-2 was highly expressed in large cell lung cancer. Both Kindlin-1 and Kindlin-2 were found not expressed or expressed at very low levels in neuroendocrine-derived small cell lung cancer. Importantly, the Kindlin-1 expression level was positively correlated with the differentiation of squamous cell lung cancer. Surprisingly, we found that the very homologous Kindlin family proteins, Kindlin-1 and Kindlin-2, displayed counteracting functional roles in lung cancer cells. Ectopic expression of Kindlin-1 in non-small-cell lung cancer cells inhibited in vitro cell migration and in vivo tumor growth, while Kindlin-2 promoted these functions. Mechanistically, Kindlin-1 prohibited epithelail to mesenchymal transition in non-small-cell lung cancer cells, while Kindlin-2 enhanced epithelail to mesenchymal transition in these cells. Taken together, we demonstrated that Kindlin-1 and Kindlin-2 differentially regulate lung cancer cell progression. Further, the expression levels of Kindlin-1 might be potentially used as a marker for lung cancer differentiation and targeting Kindlin-2 might block the invasive growth of large cell lung cancer.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education of Beijing, Beijing, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhan
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhu
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Guo
authors.forename: Yunling
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Wang
authors.forename: Guangliang
authors.initials: G
authors.lastname: Qiang
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Niu
authors.forename: Jinxia
authors.initials: J
authors.lastname: Hu
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Zhilun
authors.initials: Z
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Cui
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.forename: Weigang
authors.initials: W
authors.lastname: Fang
authors.forename: Hongquan
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C475301:FERMT1 protein, human; C477322:FERMT3 protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; C534220:kindlin-1 protein, mouse; C527802:kindlin-2 protein, mouse