Targeted proteomic analysis of small GTPases in radioresistant breast cancer cells

ABSTRACT: Radiotherapy benefits more than 50% of cancer patients and cures 40% of them, where ionizing radiation deposits energy to cells and tissues, thereby eliciting DNA damage and resulting in cell death. Small GTPases are a superfamily of proteins that play critical roles in cell signaling. Several small GTPases, including RAC1, RHOB and RALA, were previously shown to modulate radioresistance in cancer cells. However, there is no systematic proteomic study on small GTPases that regulate radioresistance in cancer cells. Herein, we applied a high-throughput scheduled multiple-reaction monitoring (MRM) method, along with the use of synthetic stable isotope-labeled peptides, to identify differentially expressed small GTPase proteins in two pairs of breast cancer cell lines, MDA-MB-231 and MCF7, and their corresponding radioresistant lines. We identified 7 commonly altered small GTPase proteins with over 1.5-fold change in the two pairs of cell lines. We also discovered ARFRP1 as a novel radioresistance regulator, where its downregulation promotes radioresistance in breast cancer cells. Together, this represents the first comprehensive assessment about the differential expression of the small GTPase proteome associated with the development of radioresistance in breast cancer cells. Our work also uncovered ARFRP1 as a new target for enhancing radiation sensitivity in breast cancer.

INSTRUMENT(S): TSQ Altis

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Breast

DISEASE(S): Breast Cancer

SUBMITTER: Zi Gao  

LAB HEAD: Yinsheng Wang

PROVIDER: PXD034360 | Pride | 2024-01-26

REPOSITORIES: Pride