Article
Altered RNA Splicing by Mutant p53 Activates Oncogenic RAS Signaling in Pancreatic Cancer.
Cancer cell - 10 Aug 2020
Escobar-Hoyos Luisa F, Penson Alex, Kannan Ram, Cho Hana, Pan Chun-Hao, Singh Rohit K, Apken Lisa H, Hobbs G Aaron, Luo Renhe, Lecomte Nicolas, Babu Sruthi, Pan Fong Cheng, Alonso-Curbelo Direna, Morris John P, Askan Gokce, Grbovic-Huezo Olivera, Ogrodowski Paul, Bermeo Jonathan, Saglimbeni Joseph, Cruz Cristian D, Ho Yu-Jui, Lawrence Sharon A, Melchor Jerry P, Goda Grant A, Bai Karen, Pastore Alessandro, Hogg Simon J, Raghavan Srivatsan, Bailey Peter, Chang David K, Biankin Andrew, Shroyer Kenneth R, Wolpin Brian M, Aguirre Andrew J, Ventura Andrea, Taylor Barry, Der Channing J, Dominguez Daniel, Kümmel Daniel, Oeckinghaus Andrea, Lowe Scott W, Bradley Robert K, Abdel-Wahab Omar, Leach Steven D
Abstract excerpt
Pancreatic ductal adenocarcinoma (PDAC) is driven by co-existing mutations in KRAS and TP53. However, how these mutations collaborate to promote this cancer is unknown. Here, we uncover sequence-specific changes in RNA splicing enforced by mutant p53 which enhance KRAS activity. Mutant p53 increases expression of splicing regulator hnRNPK to promote inclusion of cytosine-rich exons within GTPase-activating...
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