Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/180304
Title: KRAS phosphorylation regulates cell polarization and tumorigenic properties in colorectal cancer.
Author: Cabot, Débora
Brun, Sonia
Paco, Noelia
Ginesta, Mireia M.
Gendrau Sanclemente, Núria
Abuasaker, Baraa
Ruíz Fariña, Triana
Barceló, Carles
Cuatrecasas Freixas, Miriam
Bosch, Marta
Rentero Alfonso, Carles
Pons i Irazazábal, Gabriel
Estanyol i Ullate, Josep Maria
Capellá, G. (Gabriel)
Jaumot i Pijoan, Montserrat
Agell i Jané, Neus
Keywords: Càncer colorectal
Fosforilació
Colorectal cancer
Phosphorylation
Issue Date: 31-Jul-2021
Publisher: Macmillan Publishers
Abstract: Oncogenic mutations of KRAS are found in the most aggressive human tumors, including colorectal cancer. It has been suggested that oncogenic KRAS phosphorylation at Ser181 modulates its activity and favors cell transformation. Using nonphosphorylatable (S181A), phosphomimetic (S181D), and phospho-/dephosphorylatable (S181) oncogenic KRAS mutants, we analyzed the role of this phosphorylation to the maintenance of tumorigenic properties of colorectal cancer cells. Our data show that the presence of phospho-/dephosphorylatable oncogenic KRAS is required for preserving the epithelial organization of colorectal cancer cells in 3D cultures, and for supporting subcutaneous tumor growth in mice. Interestingly, gene expression differed according to the phosphorylation status of KRAS. In DLD-1 cells, CTNNA1 was only expressed in phospho-/dephosphorylatable oncogenic KRAS-expressing cells, correlating with cell polarization. Moreover, lack of oncogenic KRAS phosphorylation leads to changes in expression of genes related to cell invasion, such as SERPINE1, PRSS1,2,3, and NEO1, and expression of phosphomimetic oncogenic KRAS resulted in diminished expression of genes involved in enterocyte differentiation, such as HNF4G. Finally, the analysis, in a public data set of human colorectal cancer, of the gene expression signatures associated with phosphomimetic and nonphosphorylatable oncogenic KRAS suggests that this post-translational modification regulates tumor progression in patients.
Note: Versió postprint del document publicat a: https://doi.org/10.1038/s41388-021-01967-3
It is part of: Oncogene, 2021, vol. 40, num. 38, p. 5730-5740
URI: http://hdl.handle.net/2445/180304
Related resource: https://doi.org/10.1038/s41388-021-01967-3
ISSN: 0950-9232
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Biomedicina)

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