例如:"lncRNA", "apoptosis", "WRKY"

Interplay between c-Src and the APC/C co-activator Cdh1 regulates mammary tumorigenesis.

Nat Commun. 2019 Aug 16;10(1):3716
Tao Han 1 , Shulong Jiang 2 , Hong Zheng 3 , Qing Yin 1 , Mengyu Xie 4 , Margaret R Little 5 , Xiu Yin 6 , Ming Chen 7 , Su Jung Song 8 , Amer A Beg 9 , Pier Paolo Pandolfi 10 , Lixin Wan 11
Tao Han 1 , Shulong Jiang 2 , Hong Zheng 3 , Qing Yin 1 , Mengyu Xie 4 , Margaret R Little 5 , Xiu Yin 6 , Ming Chen 7 , Su Jung Song 8 , Amer A Beg 9 , Pier Paolo Pandolfi 10 , Lixin Wan 11
+ et al

[No authors listed]

Author information
  • 1 Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
  • 2 Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, P.R. China.
  • 3 Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
  • 4 Department of Cancer Biology PhD Program, University of South Florida, Tampa, FL, 33620, USA.
  • 5 Nova Southeastern University, Fort Lauderdale, FL, 33314, USA.
  • 6 Department of Oncology, Affiliated Jining NO.1 People's Hospital of Jining Medical University, Jining, Shandong, 272000, P.R. China.
  • 7 Department of Pathology, Duke University School of Medicine, Duke Cancer Institute, Duke University, Durham, NC, 27710, USA.
  • 8 Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Cheonan-si, Chungcheongnam-do, 31151, Republic of Korea.
  • 9 Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
  • 10 Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
  • 11 Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA. lixin.wan@moffitt.org.

摘要


The Anaphase Promoting Complex (APC) coactivator Cdh1 drives proper cell cycle progression and is implicated in the suppression of tumorigenesis. However, it remains elusive how Cdh1 restrains cancer progression and how tumor cells escape the inhibition of Cdh1. Here we report that Cdh1 suppresses the kinase activity of c-Src in an APC-independent manner. Depleting Cdh1 accelerates breast cancer cell proliferation and cooperates with PTEN loss to promote breast tumor progression in mice. Hyperactive c-Src, on the other hand, reciprocally inhibits the ubiquitin E3 ligase activity of APCCdh1 through direct phosphorylation of Cdh1 at its N-terminus, which disrupts the interaction between Cdh1 and the APC core complex. Furthermore, pharmacological inhibition of c-Src restores APCCdh1 tumor suppressor function to repress a panel of APCCdh1 oncogenic substrates. Our findings reveal a reciprocal feedback circuit of Cdh1 and c-Src in the crosstalk between the cell cycle machinery and the c-Src signaling pathway.