Abstract 2370: Depletion of p21-activated kinase 4, PAK4, inhibits cellular proliferation, motility and clonogenicity in oral squamous cell carcinoma

Abstract

Abstract Oral squamous cell carcinoma (OSCC) accounts for 90% of all malignancies in the oral cavity, and is often associated with low survival and poor prognosis. While considerable progress in OSCC treatment has been made, options for targeted therapy remain limited. Thus, it is imperative that new druggable targets are identified and characterized. p21-activated kinase 4 (PAK4) is a member of the PAK family of serine/threonine kinases, which are known modulators of a diverse range of oncogenic pathways including cell proliferation, escape from apoptosis, and anchorage-independent growth. Previous reports have indicated that PAK4 is overexpressed in a subset of invasive OSCC, and is highly associated with poor prognosis. However, the specific role of PAK4 in OSCC has yet to be elucidated. Here, we show that RNAi-mediated depletion of PAK4 conferred reduced clonogenicity, cell motility, and cell proliferation in OSCC cell lines in a cell line-dependent manner. Global proteomic profiling of PAK4-depleted H103 and H357 cells was conducted to identify the molecules and signaling pathways responsive to PAK4 depletion. In addition to reported targets of PAK4 such as CFL1, ACTB, and TUBB6, we observed that p16INK4a, pre-mRNA splicing factors (SRSF2, SRSF5, SRSF6, SLU7), and proteasome activator subunits (PSME1-4) were dysregulated as a result of PAK4 depletion. These results indicate that PAK4 plays a role in promoting OSCC progression by regulating multiple signaling pathways. Of note, there have yet to be any reports describing interactions between PAK4 signaling and mRNA splicing or proteasome activation. Further investigation is thus warranted to further delineate the potential role of PAK4 in regulating these targets. Citation Format: Felicia F. Chung, Si-Hoey Tan, Vijay J. Raja, Pei Yuen Ng, Ian C. Paterson, Chye Ling Tan, Chee-Onn Leong. Depletion of p21-activated kinase 4, PAK4, inhibits cellular proliferation, motility and clonogenicity in oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2370. doi:10.1158/1538-7445.AM2017-2370