Protein Kinase D (PKD) family contains PKD1, PKD2, and PKD3 in human. Compared to consistent tumor-suppressive functions of PKD1 in breast cancer, how PKD2/3 functions in breast cancer are not fully understood. In the current study, we found that PKD2 and PKD3 but not PKD1 were preferentially overexpressed in breast cancer and involved in regulating cell proliferation and metastasis. Integrated phosphoproteome, transcriptome, and interactome showed that PKD2 was associated with multiple cancer-related pathways, including adherent junction, regulation of actin cytoskeleton, and cell cycle-related pathways. ELAVL1 was identified as a common hub-node in networks of PKD2/3-regulated phosphoproteins and genes. Silencing ELAVL1 inhibited breast cancer growth in vitro and in vivo. Direct interaction between ELAVL1 and PKD2 or PKD3 was demonstrated. Suppression of PKD2 led to ELAVL1 translocation from the cytoplasm to the nucleus without significant affecting ELAVL1 expression. Taken together, we characterized the oncogenic functions of PKD2/3 in breast cancer and their association with cancer-related pathways, which shed lights on the oncogenic roles and mechanisms of PKDs in breast cancer.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81772956, 81572712]; National Basic Research Program of ChinaNational Basic Research Program of China [2015CB965000]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [3231005410, 3231006205, 3231006402]; Natural Science Foundation of Jiangsu ProvinceNatural Science Foundation of Jiangsu Province [BK20151403, SBK2016030027]; Six talent peaks project in Jiangsu Province [2015-JY-002]; Jiangsu Shuangchuang talent program; Nanjing Medical Science and Technique Development Foundation [QRX17061]; Jiangsu Province Post-Doctoral Fund; Science Foundation of the Chinese Academy of SciencesChinese Academy of Sciences [Y852126105]
第一作者机构：[1]Nanjing Normal Univ, Coll Life Sci, Jiangsu Key Lab Mol & Med Biotechnol, Nanjing, Jiangsu, Peoples R China[2]Southeast Univ, Inst Life Sci, Minist Educ, Key Lab Dev Genes & Human Dis, Nanjing, Jiangsu, Peoples R China[3]Chinese Acad Sci, Suzhou Inst Biomed Engn & Technol, Key Lab Biomed Diagnost, Suzhou, Peoples R China[4]Chinese Acad Sci, Changchun Inst Opt Fine Mech & Phys, Changchun, Jilin, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Nanjing Normal Univ, Coll Life Sci, Jiangsu Key Lab Mol & Med Biotechnol, Nanjing, Jiangsu, Peoples R China[2]Southeast Univ, Inst Life Sci, Minist Educ, Key Lab Dev Genes & Human Dis, Nanjing, Jiangsu, Peoples R China[7]Shanghai Jiao Tong Univ, Sch Med, Tongren Hosp, Dept Oncol, Shanghai, Peoples R China[*1]Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China.[*2]Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
推荐引用方式(GB/T 7714)：
Liu Yan,Li Jian,Ma Zhifang,et al.Oncogenic functions of protein kinase D2 and D3 in regulating multiple cancer-related pathways in breast cancer[J].CANCER MEDICINE.2019,8(2):729-741.doi:10.1002/cam4.1938.
APA：
Liu, Yan,Li, Jian,Ma, Zhifang,Zhang, Jun,Wang, Yuzhi...&Chen, Liming.(2019).Oncogenic functions of protein kinase D2 and D3 in regulating multiple cancer-related pathways in breast cancer.CANCER MEDICINE,8,(2)
MLA：
Liu, Yan,et al."Oncogenic functions of protein kinase D2 and D3 in regulating multiple cancer-related pathways in breast cancer".CANCER MEDICINE 8..2(2019):729-741
