{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:59:31Z","timestamp":1772164771962,"version":"3.50.1"},"reference-count":50,"publisher":"American Association for Cancer Research (AACR)","issue":"3","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>N-RAS is one member of a family of oncoproteins that are commonly mutated in cancer. Activating mutations in NRAS occur in a subset of colorectal cancers, but little is known about how the mutant protein contributes to the onset and progression of the disease. Using genetically engineered mice, we find that mutant N-RAS strongly promotes tumorigenesis in the context of inflammation. The protumorigenic nature of mutant N-RAS is related to its antiapoptotic function, which is mediated by activation of a noncanonical mitogen-activated protein kinase pathway that signals through STAT3. As a result, inhibition of MAP\u2013ERK kinase selectively induces apoptosis in autochthonous colonic tumors expressing mutant N-RAS. The translational significance of this finding is highlighted by our observation that NRAS mutation correlates with a less favorable clinical outcome for patients with colorectal cancer. These data show for the first time the important role that N-RAS plays in colorectal cancer.<\/jats:p>\n                  <jats:p>Significance: Little is known about N-RAS function in normal biology or in cancer. Our study links the antiapoptotic function of mutant N-RAS to its ability to promote colorectal cancer in an inflammatory context. In addition, our study pinpoints a therapeutic strategy for this distinct colorectal cancer subtype. Cancer Discov; 3(3); 294\u2013307. \u00a92013 AACR.<\/jats:p>\n                  <jats:p>This article is highlighted in the In This Issue feature, p. 239<\/jats:p>","DOI":"10.1158\/2159-8290.cd-12-0198","type":"journal-article","created":{"date-parts":[[2012,12,29]],"date-time":"2012-12-29T02:13:55Z","timestamp":1356747235000},"page":"294-307","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Mutant N-RAS Protects Colorectal Cancer Cells from Stress-Induced Apoptosis and Contributes to Cancer Development and Progression"],"prefix":"10.1158","volume":"3","author":[{"given":"Yufang","family":"Wang","sequence":"first","affiliation":[{"name":"Authors' Affiliations: 1Molecular Pathology Unit, Center for Cancer Research and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Charlestown; 2Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute; Departments of 3Medicine and 4Pathology, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts; Departments of 5Pathology and 6Medicine, Memorial Sloan-Kettering Cancer Center; 7New York University Cancer Institute, New York University School of Medicine, New York, New York; 8Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; 9Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina"}]},{"given":"S\u00e9rgia","family":"Velho","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Molecular Pathology Unit, Center for Cancer Research and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Charlestown; 2Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute; Departments of 3Medicine and 4Pathology, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts; Departments of 5Pathology and 6Medicine, Memorial Sloan-Kettering Cancer Center; 7New York University Cancer Institute, New York University School of Medicine, New York, New York; 8Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; 9Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina"}]},{"given":"Efsevia","family":"Vakiani","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Molecular Pathology Unit, Center for Cancer Research and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Charlestown; 2Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute; Departments of 3Medicine and 4Pathology, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts; Departments of 5Pathology and 6Medicine, Memorial Sloan-Kettering Cancer Center; 7New York University Cancer Institute, New York University School of Medicine, New York, New York; 8Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; 9Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina"}]},{"given":"Shouyong","family":"Peng","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Molecular Pathology Unit, Center for Cancer Research and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Charlestown; 2Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute; Departments of 3Medicine and 4Pathology, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts; Departments of 5Pathology and 6Medicine, Memorial Sloan-Kettering Cancer Center; 7New York University Cancer Institute, New York University School of Medicine, New York, New York; 8Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; 9Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina"}]},{"given":"Adam J.","family":"Bass","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Molecular Pathology Unit, Center for Cancer Research and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Charlestown; 2Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute; Departments of 3Medicine and 4Pathology, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts; Departments of 5Pathology and 6Medicine, Memorial Sloan-Kettering Cancer Center; 7New York University Cancer Institute, New York University School of Medicine, New York, New York; 8Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; 9Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina"},{"name":"Authors' Affiliations: 1Molecular Pathology Unit, Center for Cancer Research and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Charlestown; 2Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute; Departments of 3Medicine and 4Pathology, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts; Departments of 5Pathology and 6Medicine, Memorial Sloan-Kettering Cancer Center; 7New York University Cancer Institute, New York University School of Medicine, New York, New York; 8Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; 9Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina"}]},{"given":"Gerald C.","family":"Chu","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Molecular Pathology Unit, Center for Cancer Research and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Charlestown; 2Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute; Departments of 3Medicine and 4Pathology, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts; Departments of 5Pathology and 6Medicine, Memorial Sloan-Kettering Cancer Center; 7New York University Cancer Institute, New York University School of Medicine, New York, New York; 8Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; 9Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina"},{"name":"Authors' Affiliations: 1Molecular Pathology Unit, Center for Cancer Research and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Charlestown; 2Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute; Departments of 3Medicine and 4Pathology, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts; Departments of 5Pathology and 6Medicine, Memorial Sloan-Kettering Cancer Center; 7New York University Cancer Institute, New York University School of Medicine, New York, New York; 8Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; 9Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina"},{"name":"Authors' Affiliations: 1Molecular Pathology Unit, Center for Cancer Research and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Charlestown; 2Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute; Departments of 3Medicine and 4Pathology, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts; Departments of 5Pathology and 6Medicine, Memorial Sloan-Kettering Cancer Center; 7New York University Cancer Institute, New York University School of Medicine, New York, New York; 8Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; 9Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina"}]},{"given":"Jessica","family":"Gierut","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Molecular Pathology Unit, Center for Cancer Research and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Charlestown; 2Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute; Departments of 3Medicine and 4Pathology, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts; Departments of 5Pathology and 6Medicine, Memorial Sloan-Kettering Cancer Center; 7New York University Cancer Institute, New York University School of Medicine, New York, New York; 8Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; 9Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina"}]},{"given":"James M.","family":"Bugni","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Molecular Pathology Unit, Center for Cancer Research and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Charlestown; 2Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute; Departments of 3Medicine and 4Pathology, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts; Departments of 5Pathology and 6Medicine, Memorial Sloan-Kettering Cancer Center; 7New York University Cancer Institute, New York University School of Medicine, New York, New York; 8Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; 9Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina"}]},{"given":"Channing J.","family":"Der","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Molecular Pathology Unit, Center for Cancer Research and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Charlestown; 2Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute; Departments of 3Medicine and 4Pathology, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts; Departments of 5Pathology and 6Medicine, Memorial Sloan-Kettering Cancer Center; 7New York University Cancer Institute, New York University School of Medicine, New York, New York; 8Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; 9Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina"}]},{"given":"Mark","family":"Philips","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Molecular Pathology Unit, Center for Cancer Research and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Charlestown; 2Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute; Departments of 3Medicine and 4Pathology, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts; Departments of 5Pathology and 6Medicine, Memorial Sloan-Kettering Cancer Center; 7New York University Cancer Institute, New York University School of Medicine, New York, New York; 8Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; 9Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina"}]},{"given":"David B.","family":"Solit","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Molecular Pathology Unit, Center for Cancer Research and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Charlestown; 2Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute; Departments of 3Medicine and 4Pathology, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts; Departments of 5Pathology and 6Medicine, Memorial Sloan-Kettering Cancer Center; 7New York University Cancer Institute, New York University School of Medicine, New York, New York; 8Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; 9Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina"}]},{"given":"Kevin M.","family":"Haigis","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Molecular Pathology Unit, Center for Cancer Research and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Charlestown; 2Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute; Departments of 3Medicine and 4Pathology, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts; Departments of 5Pathology and 6Medicine, Memorial Sloan-Kettering Cancer Center; 7New York University Cancer Institute, New York University School of Medicine, New York, New York; 8Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; 9Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina"}]}],"member":"1086","published-online":{"date-parts":[[2013,3,7]]},"reference":[{"key":"2022060623212620200_bib1","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/nrc1097","article-title":"RAS oncogenes: the first 30 years","volume":"3","author":"Malumbres","year":"2003","journal-title":"Nat Rev Cancer"},{"key":"2022060623212620200_bib2","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1038\/sj.onc.1202174","article-title":"Increasing complexity of Ras signaling","volume":"17","author":"Campbell","year":"1998","journal-title":"Oncogene"},{"key":"2022060623212620200_bib3","first-page":"23","article-title":"GTPase 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