1. Suppression of KIF3A inhibits triple negative breast cancer growth and metastasis by repressing Rb‐E2F signaling and epithelial‐mesenchymal transition
- Author
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Runze Zhang, Xiao Wang, Weilin Wang, Fenggang Xiang, Zhimin Wei, Ning Wang, Jing Zhao, and Chengqin Wang
- Subjects
0301 basic medicine ,Cancer Research ,Cell ,Kinesins ,Triple Negative Breast Neoplasms ,medicine.disease_cause ,Metastasis ,Small hairpin RNA ,Mice ,0302 clinical medicine ,Cell Movement ,Pathology ,Triple negative breast cancer ,Neoplasm Metastasis ,Triple-negative breast cancer ,General Medicine ,Middle Aged ,Gene Expression Regulation, Neoplastic ,Retinoblastoma Binding Proteins ,Cell Transformation, Neoplastic ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Female ,Original Article ,Signal Transduction ,Epithelial-Mesenchymal Transition ,Ubiquitin-Protein Ligases ,Biology ,03 medical and health sciences ,Cell Line, Tumor ,medicine ,Animals ,Humans ,metastasis ,Gene silencing ,Epithelial–mesenchymal transition ,KIF3A ,Aged ,Cell Proliferation ,epithelial‐mesenchymal transition ,Original Articles ,medicine.disease ,Xenograft Model Antitumor Assays ,Rb‐E2F signaling ,E2F Transcription Factors ,030104 developmental biology ,Drug Resistance, Neoplasm ,Tumor progression ,Cancer research ,Carcinogenesis - Abstract
Triple negative breast cancer (TNBC) displays higher heterogeneity, stronger invasiveness, higher risk of metastasis and poorer prognosis compared with major breast cancer subtypes. KIF3A, a member of the kinesin family of motor proteins, serves as a microtubule‐directed motor subunit and has been found to regulate early development, ciliogenesis and tumorigenesis. To explore the expression, regulation and mechanism of KIF3A in TNBC, 3 TNBC cell lines, 98 cases of primary TNBC and paired adjacent tissues were examined. Immunohistochemistry, real‐time PCR, western blot, flow cytometry, short hairpin RNA (shRNA) interference, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), colony formation techniques, transwell assays, scratch tests, and xenograft mice models were used. We found that KIF3A was overexpressed in TNBC and such high KIF3A expression was also associated with tumor recurrence and lymph node metastasis. Silencing of KIF3A suppressed TNBC cell proliferation by repressing the Rb‐E2F signaling pathway and inhibited migration and invasion by repressing epithelial‐mesenchymal transition. The tumor size was smaller and the number of lung metastatic nodules was lower in KIF3A depletion MDA‐MB‐231 cell xenograft mice than in the negative control group. In addition, KIF3A overexpression correlated with chemoresistance. These results suggested that high expression of KIF3A in TNBC was associated with the tumor progression and metastasis., KIF3A,a member of kinesin super family, was over‐expressed in triple negative breast cancer (TNBC) tissues and such high KIF3A expression was associated with tumor recurrence and lymph node. Silencing of KIF3A suppressed TNBC cells proliferation, migration and invasion by repressing the Rb‐E2F signaling and EMT. And the tumor size and lung metastatic nodules were less in KIF3A depletion xenograft mice.
- Published
- 2020
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