title: SIN1 promotes the proliferation and migration of breast cancer cells by Akt activation.
abstract: Stress-activated protein kinase (SAPK) interacting protein 1 (SIN1) is an essential TORC2 component and a key regulator of Akt pathway that plays an important role in various pathological conditions including cancer. Whereas its functional role in breast cancer has not been well characterized. In the present study, SIN1 is associated with the progression and survival of breast cancer patients, as well as human breast cancer cell proliferation and migration. SIN1 mRNA level was significantly up-regulated in human breast cancer samples compared with their corresponding paracancerous histological normal tissues. Furthermore, the expression levels of SIN1 were also increased in three human breast cancer cell lines compared with human breast epithelial cell MCF10A. Overexpression of SIN1 promoted cell proliferation, colony formation and migration of breast cancer cells. Knockdown of SIN1 in MDA-MB-468 cells inhibited cell proliferation, colony formation and migration. In addition, SIN1 overexpression increased phosphorylation of Akt and knockdown of SIN1 inhibited phosphorylation of Akt in MDA-MB-468 cells. In a tumour xenograft model, overexpression of SIN1 promoted tumour growth of MDA-MB-468 cells in vivo, whereas SIN1 knockdown inhibits the tumour growth. Taken together, our results reveal that SIN1 plays an important role in breast cancer and SIN1 is a potential biomarker and a promising target in the treatment of breast cancer.
authors: Cancer Therapy Center, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.
authors: Deqiang
authors: D
authors: Wang
authors: Department of Pathology, Huai'an Maternity and Child Health Care Hospital, Huai'an, Jiangsu 223002, China.
authors: Ping
authors: P
authors: Wu
authors: Jiangsu Jiankang Vocational College, Nanjing, Jiangsu 210029, China.
authors: Hui
authors: H
authors: Wang
authors: Department of Digestive System, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, China.
authors: Lei
authors: L
authors: Zhu
authors: Clinical Laboratory, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu 210004, China zhaowei1604@163.com luyuqin1616@163.com.
authors: Wei
authors: W
authors: Zhao
authors: Department of Thyroid and Breast Surgery, The Second People's Hospital of Huai'an, Huai'an, Jiangsu 223002, China zhaowei1604@163.com luyuqin1616@163.com.
authors: Yuqin
authors: Y
authors: Lu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010766:Phosphorylation / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C493277:MAPKAP1 protein, human; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt
keywords: breast cancer; cell proliferation; human epidermal growth factor receptor 2 (HER2); migration; stress-activated protein kinase interacting protein 1 (SIN1); survival