RASSF1A inhibits PDGFB-driven malignant phenotypes of nasopharyngeal carcinoma cells in a YAP1-dependent manner

• Published in: Cell death & disease Vol. 11; no. 10; p. 855
• Main Authors: Liang, Ying-Ying, Deng, Xu-Bin, Lin, Xian-Tao, Jiang, Li-Li, Huang, Xiao-Ting, Mo, Zhi-Wen, Yuan, Ya-Wei, Teh, Muy-Teck
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.10.2020
• Subjects: 42/41; 631/67/1536; 631/67/1857; 631/67/71; 631/80/86; 64/60; 82/80; 96/100; 96/109; 96/21; 96/34; 96/35; 96/63; 96/95; Actin Cytoskeleton - metabolism; Adaptor Proteins, Signal Transducing - metabolism; Animals; Antibodies; Biochemistry; Biomarkers, Tumor - biosynthesis; Biomedical and Life Sciences; Cell Biology; Cell Culture; Cell Line, Tumor; Cell Movement - physiology; Cell Proliferation - physiology; Genes, Tumor Suppressor; Heterografts; Humans; Immunology; Life Sciences; Mice; Nasopharyngeal Carcinoma - genetics; Nasopharyngeal Carcinoma - metabolism; Nasopharyngeal Carcinoma - pathology; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - metabolism; Nasopharyngeal Neoplasms - pathology; Phenotype; Proto-Oncogene Proteins c-sis - antagonists & inhibitors; Proto-Oncogene Proteins c-sis - metabolism; Signal Transduction; Transcription Factors - metabolism; Transfection; Tumor Suppressor Proteins - biosynthesis; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-020-03054-z

Nasopharyngeal carcinoma (NPC) is a highly aggressive tumor characterized by distant metastasis. Deletion or down-regulation of the tumor suppressor protein ras-association domain family protein1 isoform A ( RASSF1A ) has been confirmed to be a key event in NPC progression; however, little is known about the effects or underlying mechanism of RASSF1A on the malignant phenotype. In the present study, we observed that RASSF1A expression inhibited the malignant phenotypes of NPC cells. Stable silencing of RASSF1A in NPC cell lines induced self-renewal properties and tumorigenicity in vivo/in vitro and the acquisition of an invasive phenotype in vitro. Mechanistically, RASSF1A inactivated Yes-associated Protein 1 (YAP1), a transcriptional coactivator, through actin remodeling, which further contributed to Platelet Derived Growth Factor Subunit B ( PDGFB ) transcription inhibition. Treatment with ectopic PDGFB partially increased the malignancy of NPC cells with transient knockdown of YAP1. Collectively, these findings suggest that RASSF1A inhibits malignant phenotypes by repressing PDGFB expression in a YAP1-dependent manner. PDGFB may serve as a potential interest of therapeutic regulators in patients with metastatic NPC.