HOXD8 inhibits the proliferation and migration of triple-negative breast cancer cells and induces apoptosis in them through regulation of AKT/mTOR pathway |
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| Institution: | 1. Department of Thyroid and Breast Surgery, the Affiliated Peoples Hospital of Ningbo University, Ningbo City, Zhejiang Province, 315040, China;2. Department of Nail Breast Surgery, Huai''an Second People''s Hospital, Huai''an City, Jiangsu Province, 223002, China;1. CNRS, IFCE, INRAE, Université de Tours, PRC, 37380, Nouzilly, France;2. Union Evolution, Noyal-Sur-Vilaine, France;3. INRAE, Université de Tours, CHU de Tours, PIXANIM, 37380 Nouzilly, France;4. INRAE, Université de Tours, ISP, 37380 Nouzilly, France;5. Tours University, Tours, France;1. Key Laboratory of Brain Functional Genomics (Ministry of Education and Shanghai), School of Life Sciences, East China Normal University, Shanghai, China;2. Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China;1. Centre for Human Reproductive Science (ChRS), Institute of Metabolism and Systems Research, College of Medical & Dental Sciences, University of Birmingham, United Kingdom;2. Birmingham Women’s Fertility Centre, Birmingham Women’s Hospital, Birmingham Women’s and Children’s Hospital NHS Foundation Trust, Birmingham, United Kingdom;3. School of Biosciences, University of Birmingham, United Kingdom;1. Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China;2. Department of Biochemistry and Molecular Biology, GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China;1. Department of Obstetrics, The Maternity Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, China;2. Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China;3. Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China;4. The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China;5. Guangxi Key Laboratory of Genomic and Personalized Medicine, Nanning, Guangxi, 530021, China;6. Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, 530021, China;1. Department of Assisted Reproduction, The Ninth People''s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China;2. Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, Hong Kong, China;3. IVF Unit, Department of Obstetrics and Gynecology, Sheba Medical Center, Tel- Hashomer and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel |
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| Abstract: | HOXD8 (Homeobox D8) functions as an apoptotic inducer to suppress tumor progression. However, the role of HOXD8 in triple-negative breast cancer (TNBC) has not been fully understood. Firstly, HOXD8 was found to be reduced in TNBC tissues based on the TCGA samples through Ualcan (http://ualcan.path.uab.edu/analysis.html) prediction. Moreover, data from qRT-PCR and western blot confirmed the lower expression of HOXD8 in the TNBC tissues or cells than that in paracancerous tissues or human mammary epithelial cell line (MCF10A), respectively. Secondly, pcDNA-mediated over-expression of HOXD8 were conducted in TNBC cells, and the gain-of functional assays showed that over-expression of HOXD8 promoted TNBC cell progression with repressed cell apoptosis and induced proliferation, migration and invasion. Moreover, xenografted mouse model was constructed by injection of tumor cell line with stable over-expression of HOXD8 to assess the in vivo tumor growth, and the results revealed that over-expression of HOXD8 inhibited tumor growth. Lastly, our results showed that AKT and mTOR phosphorylation were repressed by HOXD8 over-expression in TNBC cells. In conclusion, HOXD8 functioned as an apoptotic inducer to suppress TNBC cell growth and progression by inhibition of AKT/mTOR pathway. |
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| Keywords: | HOXD8 TNBC Apoptosis Progression AKT/mTOR |
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