biostudies-literatureQi XBLRD VA4269-82https://www.ebi.ac.uk/biostudies/studies/S-EPMC4147322biostudies-literatureUnknown5(12)A cancer phenotype is driven by several proteins and targeting a cluster of functionally interdependent molecules should be more effective for therapeutic intervention. This is specifically important for Ras-dependent cancer, as mutated (MT) Ras is non-druggable and targeting its interaction with effectors may be essential for therapeutic intervention. Here, we report that a protein-complex activated by the Ras effector p38γ MAPK is a novel therapeutic target for K-Ras-dependent colon cancer. Unbiased proteomic screening and immune-precipitation analyses identified p38γ interaction with heat shock protein 90 (Hsp90) and K-Ras in K-Ras MT, but not wild-type (WT), colon cancer cells, indicating a role of this complex in Ras-dependent growth. Further experiments showed that this complex requiOncotargetIdentification of a ternary protein-complex as a therapeutic target for K-Ras-dependent colon cancer.PMC4147322I01 BX002883Li GChesnik MATsai SChen GDong LHou SLepp ABasir ZSzabo AMirza SPQi XWu SYin NXie CfalseIdentification of a ternary protein-complex as a therapeutic target for K-Ras-dependent colon cancer.A cancer phenotype is driven by several proteins and targeting a cluster of functionally interdependent molecules should be more effective for therapeutic intervention. This is specifically important for Ras-dependent cancer, as mutated (MT) Ras is non-druggable and targeting its interaction with effectors may be essential for therapeutic intervention. Here, we report that a protein-complex activated by the Ras effector p38γ MAPK is a novel therapeutic target for K-Ras-dependent colon cancer. Unbiased proteomic screening and immune-precipitation analyses identified p38γ interaction with heat shock protein 90 (Hsp90) and K-Ras in K-Ras MT, but not wild-type (WT), colon cancer cells, indicating a role of this complex in Ras-dependent growth. Further experiments showed that this complex requi2014-01-01T00:00:00Z2014 Jun2025-04-22T16:52:25.471Z2019-03-27T01:34:48ZS-EPMC41473222496221310.18632/oncotarget.2001