2. Academic Validation
  3. WDR63 inhibits Arp2/3-dependent actin polymerization and mediates the function of p53 in suppressing metastasis

WDR63 inhibits Arp2/3-dependent actin polymerization and mediates the function of p53 in suppressing metastasis

  • EMBO Rep. 2020 Apr 3;21(4):e49269. doi: 10.15252/embr.201949269.
Kailiang Zhao 1,  Decai Wang 2,  Xiaolong Zhao 2,  Chenfeng Wang 1,  Yongxiang Gao 2,  Kaiyue Liu 1,  Fang Wang 1,  Xianning Wu 3,  Xuejuan Wang 2,  Linfeng Sun 2,  Jianye Zang 2,  Yide Mei 1
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Hefei National Laboratory for Physical Sciences at Microscale, Division of Lifesciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
  • 2 School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
  • 3 Department of Thoracic Surgery, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China.
PMID: 32128961 DOI: 10.15252/embr.201949269
Abstract

Accumulating evidence suggests that p53 plays a suppressive role in Cancer metastasis, yet the underlying mechanism remains largely unclear. Regulation of actin dynamics is essential for the control of cell migration, which is an important step in metastasis. The Arp2/3 complex is a major nucleation factor to initiate branched actin polymerization that drives cell migration. However, it is unknown whether p53 could suppress metastasis through modulating Arp2/3 function. Here, we report that WDR63 is transcriptionally upregulated by p53. We show with migration assays and mouse xenograft models that WDR63 negatively regulates cell migration, invasion, and metastasis downstream of p53. Mechanistically, WDR63 interacts with the Arp2/3 complex and inhibits Arp2/3-mediated actin polymerization. Furthermore, WDR63 overexpression is sufficient to dampen the increase in cell migration, invasion, and metastasis induced by p53 depletion. Together, these findings suggest that WDR63 is an important player in the regulation of Arp2/3 function and also implicate WDR63 as a critical mediator of p53 in suppressing metastasis.

Keywords

Arp2/3; WDR63; metastasis; p53.

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