title: The tumor suppressor RASSF10 is upregulated upon contact inhibition and frequently epigenetically silenced in cancer.
abstract: The Ras association domain family (RASSF) comprises a group of tumor suppressors that are frequently epigenetically inactivated in various tumor entities and linked to apoptosis, cell cycle control and microtubule stability. In this work, we concentrated on the newly identified putative tumor suppressor RASSF10. Methylation analysis reveals RASSF10 promoter hypermethylation in lung cancer, head and neck (HN) cancer, sarcoma and pancreatic cancer. An increase in RASSF10 methylation from normal tissues, primary tumors to cancer cell lines was observed. Methylation was reversed by 5-aza-2'-deoxycytidine treatment leading to reexpression of RASSF10. We further show that overexpression of RASSF10 suppresses colony formation in cancer cell lines. In addition, RASSF10 is upregulated by cell-cell contact and regulated on promoter level as well as endogenously by forskolin, protein kinase A (PKA) and activator Protein 1 (AP-1), linking RASSF10 to the cAMP signaling pathway. Knockdown of the AP-1 member JunD interfered with contact inhibition induced RASSF10 expression. In summary, we found RASSF10 to be epigenetically inactivated by hypermethylation of its CpG island promoter in lung, HN, sarcoma and pancreatic cancer. Furthermore, our novel findings suggest that tumor suppressor RASSF10 is upregulated by PKA and JunD signaling upon contact inhibition and that RASSF10 suppresses growth of cancer cells.
authors.affiliation: Institute for Genetics, Justus-Liebig-University, Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Giessen, Germany.
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authors.lastname: Würl
authors.forename: H
authors.initials: H
authors.lastname: Taubert
authors.forename: R H
authors.initials: RH
authors.lastname: Dammann
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