Abstract LB213: ACTL6A (Actin-like Protein 6A) enhances the cancer phenotype

Abstract

Abstract Epidermal squamous cell carcinoma (SCC) is an extremely common, invasive and metastatic cancer. ACTL6A, an important protein subunit of the SWI/SNF epigenetic regulatory complex, is frequently overexpressed in cancer cells. In the present study, we show that ACTL6A drives SCC cell proliferation, invasion, migration and tumor formation, and that this aggressive phenotype is markedly reduced in ACTL6A knockdown cells. Expression of ACTL6A is associated with reduced p21Cip1 level and treatment with ACTL6A-siRNA results in a marked increase in p21Cip1 and attenuation of the cancer phenotype. Molecular studies reveal that ACTL6A suppresses p21Cip1 promoter activity to reduce mRNA and p21Cip1 protein and that loss of p21Cip1 expression appears to be biologically meaningful, as p21Cip1 knockdown enhances the aggressive phenotype. ACTL6A suppression of p21Cip1 expression requires the p53 and Sp1 transcription response elements in the p21Cip1 gene promoter. In addition, ACTL6A knockdown results in increased p53 tumor suppressor expression. These studies show that ACTL6A facilitates an aggressive cancer phenotype by reducing p53 and p21Cip1 mRNA and protein and suggests that ACTL6A contributes to an aggressive cancer phenotype in epidermal squamous cell carcinoma. Citation Format: Suruchi Shrestha, Gautam Adhikary, Wen Xu, Sivaveera Kandaysamy, Richard L. Eckert. ACTL6A (Actin-like Protein 6A) enhances the cancer phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB213.