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Suppression of KIF3A inhibits triple negative breast cancer growth and metastasis by repressing Rb-E2F signaling and epithelial-mesenchymal transition.
Wang, Weilin; Zhang, Runze; Wang, Xiao; Wang, Ning; Zhao, Jing; Wei, Zhimin; Xiang, Fenggang; Wang, Chengqin.
Afiliação
  • Wang W; Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao, China.
  • Zhang R; Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao, China.
  • Wang X; Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao, China.
  • Wang N; Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • Zhao J; Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao, China.
  • Wei Z; Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • Xiang F; Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • Wang C; Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao, China.
Cancer Sci ; 111(4): 1422-1434, 2020 Apr.
Article em En | MEDLINE | ID: mdl-32011034
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cinesinas / Ubiquitina-Proteína Ligases / Fatores de Transcrição E2F / Proteínas de Ligação a Retinoblastoma / Neoplasias de Mama Triplo Negativas Tipo de estudo: Prognostic_studies Limite: Aged / Animals / Female / Humans / Middle aged Idioma: En Revista: Cancer Sci Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cinesinas / Ubiquitina-Proteína Ligases / Fatores de Transcrição E2F / Proteínas de Ligação a Retinoblastoma / Neoplasias de Mama Triplo Negativas Tipo de estudo: Prognostic_studies Limite: Aged / Animals / Female / Humans / Middle aged Idioma: En Revista: Cancer Sci Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China