title: Kindlin-2 interacts with β-catenin and YB-1 to enhance EGFR transcription during glioma progression.
abstract: Kindlin-2 promotes carcinogenesis through regulation of cell-cell and cell-extracellular matrix adhesion. However, the role of Kindlin-2 in glioma has not been elucidated. We investigated Kindlin-2 expression in 188 human glioma tissue samples. High Kindlin-2 expression was correlated with high pathological grade and a worse prognosis. Kindlin-2 promoted glioma cell motility and proliferation both in vitro and in vivo. Importantly, Kindlin-2 activated the EGFR pathway and increased EGFR mRNA levels. In addition to up-regulating Y-box binding protein-1 (YB-1) and β-catenin expression, Kindlin-2 formed a transcriptional complex with YB-1 and β-catenin that bound to the EGFR promoter and enhanced transcription. The β-catenin/YB-1/EGFR pathway was required for Kindlin-2-mediated functions. Our data provide a better understanding of the mechanisms underlying glioma progression, and suggest that Kindlin-2 may be a biomarker and therapeutic target in glioma.
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.|State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.|Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.|Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China.|China National Clinical Research Center for Neurological Diseases, Beijing 100050, China.
authors.forename: Yunwei
authors.initials: Y
authors.lastname: Ou
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Zitong
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Qingnan
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261, USA.|Department of Biology and Shenzhen Key Laboratory of Cell Microenvironment, South University of Science and Technology of China, Shenzhen, 518055, China.
authors.forename: Chuanyue
authors.initials: C
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Fu
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Ji
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Jiaji
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China.
authors.forename: Chunjiang
authors.initials: C
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Song
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015398:Signal Transduction; D014158:Transcription, Genetic; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism*; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C477322:FERMT3 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D051176:beta Catenin; D066246:ErbB Receptors
keywords: EGFR; Kindlin-2; glioma; transcription