STOP gene Phactr4 is a tumor suppressor

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 5; pp. E407 - E414
• Main Authors: Solimini, Nicole L, Liang, Anthony C, Xu, Chunxiao, Pavlova, Natalya N, Xu, Qikai, Davoli, Teresa, Li, Mamie Z, Wong, Kwok-Kin, Elledge, Stephen J
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 29-01-2013; National Acad Sciences
• Series: PNAS Plus
• Subjects: Animals; Biological Sciences; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Transformed; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic - genetics; Cells; Cells, Cultured; Doxycycline - pharmacology; Epigenetics; Female; Gene Expression Regulation, Neoplastic - drug effects; Humans; Immunoblotting; Mammary Glands, Human - cytology; Mammary Glands, Human - metabolism; Mammary Neoplasms, Experimental - genetics; Mammary Neoplasms, Experimental - metabolism; Mammary Neoplasms, Experimental - pathology; MCF-7 Cells; Mice; Mice, Inbred BALB C; Mice, Nude; Mutation; Phosphorylation; PNAS Plus; Proteins; RNA Interference; Transfection; Transplantation, Heterologous; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1221385110

Significance Cell proliferation control is central to tumor suppression. We previously identified hundreds of suppressors of tumorigenesis and/or proliferation (STOP) genes that restrain normal cell proliferation. Here we show that one such STOP gene, phosphatase and actin regulator 4 (PHACTR4), acts to prevent tumorigenesis. Phactr4 suppresses proliferation and transformation in vitro and tumorigenesis in vivo. PHACTR4 is significantly mutated or downregulated in several cancers, and reintroduction of Phactr4 limits proliferation and tumor growth in cells from these cancers. Thus, our studies provide strong evidence that PHACTR4 is a tumor suppressor.