title: BKCa promotes growth and metastasis of prostate cancer through facilitating the coupling between αvβ3 integrin and FAK.
abstract: BKCa is a large conductance calcium activated potassium channel promoting prostate cancer cell proliferation, although the mechanism is not fully elucidated. In addition, whether BKCa is involved in metastasis of prostate cancer remains to be explored. Here, we report that BKCa is overexpressed in prostate cancer. BKCa expression positively correlates with Ki67 index and gleason score of prostate cancer. Upregulation of BKCa promoted proliferation, migration and invasion of prostate cancer cells. On the contrary, downregulation of BKCa inhibited growth and metastasis of prostate cancer cells both in vitro and in vivo. Moreover, the ion-conducting function of BKCa contributed moderately to prostate cancer proliferation and migration, although, this was not the primary mechanism. BKCa action was mainly mediated through forming a functional complex with αvβ3 integrin. The BKCa/αvβ3 integrin complex promoted FAK phosphorylation independent of the channel activity. Overexpression of BKCa enhanced its association with αvβ3 integrin and FAK which increased FAK phosphorylation. Conversely, disrupting the complex by downregulation of BKCa reduced FAK phosphorylation. Finally, blocking of αvβ3 integrin or p-FAK activity using LM609 or Y15 markedly abrogated BKCa-enhanced cell proliferation and migration. Taken together, these results suggest that targeting BKCa/αvβ3/FAK may inaugurate innovative approaches to inhibit prostate cancer growth and metastasis.
authors.affiliation: Department of Oncology, General Hospital of Shenyang Military Area Command, Shenyang, P. R. China.|Department of Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, P. R. China.|Department of Aerospace Medicine, Fourth Military Medical University, Xi'an, P. R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of Oncology, General Hospital of Shenyang Military Area Command, Shenyang, P. R. China.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, P. R. China.
authors.forename: Danqi
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Aerospace Medicine, Fourth Military Medical University, Xi'an, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Gynaecology and Obstetrics, First Affiliated Hospital, Jilin University, Jilin, P. R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Urology, PLA 105 Hospital, Hefei, P. R. China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Oncology, General Hospital of Shenyang Military Area Command, Shenyang, P. R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, P. R. China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Oncology, General Hospital of Shenyang Military Area Command, Shenyang, P. R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Aerospace Medicine, Fourth Military Medical University, Xi'an, P. R. China.
authors.forename: Manjiang
authors.initials: M
authors.lastname: Xie
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D039302:Integrin alphaVbeta3; C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
keywords: BKCa; FAK; integrin αvβ3; metastasis; prostate cancer