2. Academic Validation
  3. Oncogene PRR14 promotes breast cancer through activation of PI3K signal pathway and inhibition of CHEK2 pathway

Oncogene PRR14 promotes breast cancer through activation of PI3K signal pathway and inhibition of CHEK2 pathway

  • Cell Death Dis. 2020 Jun 15;11(6):464. doi: 10.1038/s41419-020-2640-8.
Xiaolei Ren  # 1 2,  Meijun Long  # 3,  Zhihong Li 1 2,  Boda Wu 4 5,  Tao Jin 4 6,  Chao Tu 1 2,  Lin Qi 1 2,  Mei Yang 7 8
Affiliations

Affiliations

  • 1 Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, China.
  • 2 Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.
  • 3 Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
  • 4 Department of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, China.
  • 5 Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, China.
  • 6 Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
  • 7 Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, China. [email protected].
  • 8 Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, Changsha, China. [email protected].
  • # Contributed equally.
PMID: 32541902 DOI: 10.1038/s41419-020-2640-8
Abstract

Nuclear envelope component PRR14 has been detected to be upregulated in varieties of cancers, especially in breast Cancer. But its role in breast carcinogenesis is poorly understood. In this study, we show PRR14 contributes to breast carcinogenesis mainly through overexpression, which derives from elevated transcription and gene amplification. Increased PRR14 expression promotes breast Cancer cell proliferation and tumor formation. Biochemical analysis reveals, in addition to previously reported activation of PI3-kinase/Akt/mTOR pathway, PRR14 overexpression regulates cell cycle in breast Cancer by inhibiting CHEK2's activation, followed with the deregulation of DNA damage pathway. In correspondence, CHEK2 and PRR14 show opposite impact on breast Cancer patients receiving chemotherapy. Collectively, our study is the first to document the oncogenetic role of PRR14 in breast Cancer, which protects cells from Apoptosis and stimulates proliferation by activating the PI3-kinase/Akt/mTOR pathway and inhibiting the CHEK2 pathway. Both of these pathways are of great influence in breast Cancer and PRR14 appears to be their novel interacting node, which renders patients more resistance to chemotherapy and provides a potential therapeutic target in breast Cancer.

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