Suppression of motor protein KIF3C expression inhibits tumor growth and metastasis in breast cancer by inhibiting TGF-β signaling.
Breast cancer is the most common cause of death among women. KIF3C, a member of kinesin superfamily, functions as a motor protein involved in axonal transport in neuronal cells. To explore the expression, regulation and mechanism of KIF3C in breast cancer, 4 breast cancer cell lines and 93 cases of primary breast cancer and paired adjacent tissues were examined. Immunohistochemistry, Real Time Polymerase Chain Reaction (RT-PCR), Western blot, flow cytometry, short hairpin RNA (shRNA) interference, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation techniques and xenograft mice model were used. We found that KIF3C was over-expressed in breast cancer tissues and such high KIF3C expression was also associated with tumor recurrence and lymph node metastasis. Silencing of KIF3C by shRNA inhibited epithelial-mesenchymal transition and metastasis by inhibiting TGF-β signaling and suppressed breast cancer cell proliferation through inducing G2/M phase arrest. The tumor size was smaller and the number of lung metastatic nodules was less in KIF3C depletion MDA-MB-231 cell xenograft mice than in negative control group. These results suggested that high expression of KIF3C in breast cancer may be associated with the tumor progression and metastasis.
Department of Pathology, Medical College of Qingdao University, Qingdao, China. Electronic address: wangcq1121@126.com.
Chengqin
C
Wang
Department of Emergency, Binzhou Center Hospital, Binzhou, China.
Chenggang
C
Wang
Department of Pathology, the Affiliated Hospital of Qingdao University, Qingdao, China.
Zhimin
Z
Wei
Department of Pathology, the Affiliated Hospital of Qingdao University, Qingdao, China.
Yujun
Y
Li
Department of Pathology, Medical College of Qingdao University, Qingdao, China.
Wenhong
W
Wang
Department of Pathology, the Affiliated Hospital of Qingdao University, Qingdao, China.
Xia
X
Li
Department of Pathology, the Affiliated Hospital of Qingdao University, Qingdao, China.
Jing
J
Zhao
Department of Pathology, the Affiliated Hospital of Qingdao University, Qingdao, China.
Xuan
X
Zhou
Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, China.
Xun
X
Qu
Department of Pathology, Medical College of Qingdao University, Qingdao, China; Department of Pathology, the Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address: wcq7618@126.com.
Fenggang
F
Xiang
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D047368:Tumor Burden
C110520:KIF3C protein, human; D016212:Transforming Growth Factor beta; D016547:Kinesins
Breast cancer; KIF3C; Metastasis; TGF-β signaling; shRNA