American Association for Cancer Research
Browse
00085472can162060-sup-168026_1_supp_3689587_22hrv6.pptx (49.21 MB)

Supplementary Figures 4-6 from Plk4 Promotes Cancer Invasion and Metastasis through Arp2/3 Complex Regulation of the Actin Cytoskeleton

Download (49.21 MB)
figure
posted on 2023-03-31, 01:01 authored by Karineh Kazazian, Christopher Go, Hannah Wu, Olga Brashavitskaya, Roland Xu, James W. Dennis, Anne-Claude Gingras, Carol J. Swallow

Fig S4. Plk4 overexpression increases U2OS migration. Fig S5. Plk4 regulates HeLa invasion and spreading. Fig S6. Persistent Plk4 knockdown in MDA-MB-231 cells using a lentiviral shRNA system.

Funding

Cancer Research Society

CIHR

Syd Cooper Program for the Prevention of Cancer Progression

Canada Research Chair in Functional Proteomics and the Lea Reichmann Chair in Cancer Proteomics

Johnson Medical Products Surgeon and Canadian Society of Surgical Oncology Research

History

ARTICLE ABSTRACT

The polo family serine threonine kinase Plk4 has been proposed as a therapeutic target in advanced cancers based on increased expression in primary human cancers, facilitation of tumor growth in murine xenograft models, and centrosomal amplification induced by its overexpression. However, both the causal link between these phenomena and the feasibility of selective Plk4 inhibition remain unclear. Here we characterize Plk4-dependent cancer cell migration and invasion as well as local invasion and metastasis of cancer xenografts. Plk4 depletion suppressed cancer invasion and induced an epithelial phenotype in poorly differentiated breast cancer cells. In an unbiased BioID screen for Plk4 interactors, we identified members of the Arp2/3 complex and confirmed a physical and functional interaction between Plk4 and Arp2 in mediating Plk4-driven cancer cell movement. This interaction is mediated through the Plk4 Polo-box 1-Polo-box 2 domain and results in phosphorylation of Arp2 at the T237/T238 activation site, which is required for Plk4-driven cell movement. Our results validate Plk4 as a therapeutic target in cancer patients and reveal a new role for Plk4 in regulating Arp2/3-mediated actin cytoskeletal rearrangement. Cancer Res; 77(2); 434–47. ©2016 AACR.