Protein Folding Stability Profiling of Colorectal Cancer Chemoresistance Identifies Functionally Relevant BiomarkersClick to copy article linkArticle link copied!
- Baiyi QuanBaiyi QuanDepartment of Chemistry, Duke University, Durham, North Carolina 27708-0346, United StatesMore by Baiyi Quan
- Morgan A. BaileyMorgan A. BaileyDepartment of Chemistry, Duke University, Durham, North Carolina 27708-0346, United StatesMore by Morgan A. Bailey
- John MantyhJohn MantyhDepartment of Medicine, Duke University Medical Center, Durham, North Carolina 27710, United StatesMore by John Mantyh
- David S. HsuDavid S. HsuDepartment of Medicine, Duke University Medical Center, Durham, North Carolina 27710, United StatesMore by David S. Hsu
- Michael C. Fitzgerald*Michael C. Fitzgerald*Email: [email protected]Department of Chemistry, Duke University, Durham, North Carolina 27708-0346, United StatesMore by Michael C. Fitzgerald
Abstract
![Abstract Image](/cms/10.1021/acs.jproteome.3c00045/asset/images/medium/pr3c00045_0007.gif)
Reported here is the application of three protein folding stability profiling techniques (including the stability of proteins from rates of oxidation, thermal protein profiling, and limited proteolysis approaches) to identify differentially stabilized proteins in six patient-derived colorectal cancer (CRC) cell lines with different oxaliplatin sensitivities and eight CRC patient-derived xenografts (PDXs) derived from two of the patient derived cell lines with different oxaliplatin sensitivities. Compared to conventional protein expression level analyses, which were also performed here, the stability profiling techniques identified both unique and novel proteins and cellular components that differentiated the sensitive and resistant samples including 36 proteins that were differentially stabilized in at least two techniques in both the cell line and PDX studies of oxaliplatin resistance. These 36 differentially stabilized proteins included 10 proteins previously connected to cancer chemoresistance. Two differentially stabilized proteins, fatty acid synthase and elongation factor 2, were functionally validated in vitro and found to be druggable protein targets with biological functions that can be modulated to improve the efficacy of CRC chemotherapy. These results add to our understanding of CRC oxaliplatin resistance, suggest biomarker candidates for predicting oxaliplatin sensitivity in CRC, and inform new strategies for overcoming chemoresistance in CRC.
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