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Proximity Mapping of the ER Proteome Reveals Metastasis-specific Candidate Biomarkers in Breast Cancer Cell Lines
Mehmet Sarihan1, Elifcan Kocyigit2, Murat Kasap2
1Proteomics Laboratory, Department of Medical Biology, Faculty of Medicine, Kocaeli University, Kocaeli, Türkiye mehmet.sarihan@kocaeli.edu.tr.
Background/Aim:
Breast cancer is the most frequently diagnosed cancer among women. While biomarkers are critical for early detection and therapy, current markers lack sufficient specificity and sensitivity. The endoplasmic reticulum (ER) plays a central role in protein folding, post-translational modification, and lipid metabolism, and its alterations are linked to tumor progression. This study aimed to map ER proteome changes associated with breast cancer invasiveness and identify novel candidate biomarkers.
Materials And Methods:
We compared the ER proteomes of non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cell lines using an ER-targeted TurboID proximity labelling approach, followed by LC-MS/MS analysis. Bioinformatic analyses were performed to determine functional associations and differential expression related to invasion and metastasis for the candidate biomarkers.
Results:
A total of 2,079 proteins were identified, including 1,378 ER proteins. Analysis revealed that more than four hundred ER-resident or associated proteins were differentially regulated in invasive MDA-MB-231, many of which were linked to invasion and metastasis. Upregulated proteins were involved in cellular localization, ECM remodeling, cell mobility, adhesion, vesicle trafficking, and ER stress, whereas downregulated proteins were primarily associated with energy metabolism. Additionally, in this study, 36 ER-associated proteins were identified for the first time as candidates linked to breast cancer, highlighting their potential as novel biomarkers and therapeutic targets.
Conclusion:
ER-targeted TurboID proximity labelling effectively maps the proteomic landscape of breast cancer cells, revealing functional adaptations that support invasive and metastatic phenotypes. Notably, 36 ER proteins were identified as novel candidates not previously linked to breast cancer, highlighting new potential biomarkers and therapeutic targets. These findings provide valuable insights into ER proteome remodeling, offering avenues for understanding breast cancer progression and strategies to prevent metastasis.
