Clinical proteomics of invasive breast carcinoma reveals a major role for proline metabolism in imparting drug resistance

ABSTRACT: Aggressive breast tumors are routinely treated with pre-operative chemotherapy. However, a subset of patients have recurrence despite adjuvant treatment. To identify metabolic processes involved in drug resistance, we took a mass spectrometry-based proteomic approach, and analyzed a breast cancer cohort of 113 samples comprising of breast tumors before and after chemotherapy, with matched tumor adjacent normal tissue from partial responders that underwent neoadjuvant treatment (NAT). Pattern analysis of 7180 proteins revealed more than 1000 proteins with significantly differential expression in primary tumor relative to the healthy tissue, which do not respond to treatment, in treatment resistant patients. Among those, we found significant upregulation of the proline biosynthesis pathway, primarily, PYCR1 that significantly correlated with lower recurrence free survival time in our cohort. Functional analysis showed that PYCR1 induced a pro-survival effect upon treatment with chemotherapy drugs thus emphasizing the potential role of PYCR1 in drug resistance in advanced breast cancer.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Breast Invasive Ductal Carcinoma Cell

DISEASE(S): Breast Cancer

SUBMITTER: Tamar Geiger  

LAB HEAD: Tamar Geiger

PROVIDER: PXD012000 | Pride | 2020-08-24

REPOSITORIES: Pride