دورية أكاديمية
KRAS phosphorylation regulates cell polarization and tumorigenic properties in colorectal cancer.
| العنوان: | KRAS phosphorylation regulates cell polarization and tumorigenic properties in colorectal cancer. |
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| المؤلفون: | Cabot D; Department Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Brun S; Department Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Paco N; Department Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Ginesta MM; Hereditary Cancer Program, Translational Research Laboratory, Catalan Institute of Oncology, ICO-IDIBELL, Hospitalet de Llobregat, Barcelona, Spain and Centro de Investigación Biomédica en Red en Cáncer (CIBERONC), Madrid, Spain., Gendrau-Sanclemente N; Department Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.; Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, Hospital Duran i Reynals, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain., Abuasaker B; Department Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Ruiz-Fariña T; Department Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain., Barceló C; Department Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.; Institut d'Investigació Sanitària Illes Balears (IdISBa), Palma de Mallorca, Spain., Cuatrecasas M; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.; Departament de Fonaments Clínics, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona; Pathology Department and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) and Tumor Bank-Biobank, Hospital Clínic, Barcelona, Spain., Bosch M; Department Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Rentero C; Department Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Pons G; Departament de Ciències Fisiològiques, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona and Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain., Estanyol JM; Department Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.; Proteomics Unit, CCiT-UB, Universitat de Barcelona, Barcelona, Spain., Capellà G; Hereditary Cancer Program, Translational Research Laboratory, Catalan Institute of Oncology, ICO-IDIBELL, Hospitalet de Llobregat, Barcelona, Spain and Centro de Investigación Biomédica en Red en Cáncer (CIBERONC), Madrid, Spain., Jaumot M; Department Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain. mjaumot@ub.edu.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. mjaumot@ub.edu., Agell N; Department Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain. neusagell@ub.edu.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. neusagell@ub.edu. |
| المصدر: | Oncogene [Oncogene] 2021 Sep; Vol. 40 (38), pp. 5730-5740. Date of Electronic Publication: 2021 Jul 31. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5594 (Electronic) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2002->: Basingstoke : Nature Publishing Group Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987- |
| مواضيع طبية MeSH: | Colorectal Neoplasms/*pathology , Proto-Oncogene Proteins p21(ras)/*genetics , Proto-Oncogene Proteins p21(ras)/*metabolism, Animals ; Cell Line, Tumor ; Cell Polarity ; Cell Proliferation ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Gene Expression Regulation, Neoplastic ; HCT116 Cells ; Humans ; MAP Kinase Signaling System ; Mice ; Mutation ; Neoplasm Transplantation ; Nerve Tissue Proteins/genetics ; Phosphorylation ; Plasminogen Activator Inhibitor 1/genetics ; Receptors, Cell Surface/genetics ; Trypsin/genetics ; Trypsinogen/genetics |
| مستخلص: | 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. (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.) |
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| المشرفين على المادة: | 0 (KRAS protein, human) 0 (NEO1 protein, human) 0 (Nerve Tissue Proteins) 0 (Plasminogen Activator Inhibitor 1) 0 (Receptors, Cell Surface) 0 (SERPINE1 protein, human) 103964-84-7 (PRSS2 protein, human) 9002-08-8 (Trypsinogen) EC 3.4.21.4 (PRSS1 protein, human) EC 3.4.21.4 (PRSS3 protein, human) EC 3.4.21.4 (Trypsin) EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) |
| تواريخ الأحداث: | Date Created: 20210801 Date Completed: 20211230 Latest Revision: 20230206 |
| رمز التحديث: | 20230206 |
| DOI: | 10.1038/s41388-021-01967-3 |
| PMID: | 34333552 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1476-5594 |
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| DOI: | 10.1038/s41388-021-01967-3 |