Abstract
Poor prognosis due to the high relapse and metastasis rates of breast cancer has been particularly linked to the luminal B subtype. The current study utilized MCF-7 and ZR-75-1 to investigate various luminal subtypes of breast cancers that have discrepant expressions in the estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Understanding of the differential protein profiles and the associated pathways could help alleviate the malignance and promote the long-term survival rate of breast cancer patients. Functional proteome tools were applied to comprehensively delineate the global protein alterations that reflect the varieties of biological features between the two subtypes. In this study, a total of 11 proteins with significant and meaningful changes were identified. These protein targets including PRX2, CK19, nucleophosmin and cathepsin D were mostly involved in cell differentiation or proliferation. Particularly, cathepsin D was highly expressed in the luminal B subtype. Moreover, the level of cathepsin-D was also upregulated in the clinical metastatic tissues. Accordingly, the RNA interference-mediated silencing of cathepsin D stimulated ER expression but suppressed the level of HER2. The knockdown of cathepsin D enhanced the level of ZO-1 and a remarkable decrease in N-cadherin was also detected. Again, the matrix metalloproteinases (MMP) activity was impaired under the cathepsin D abolishment. Collectively, this study represented a modality to explore novel relationships in a proteome complex and highlighted the functional roles of cathepsin D in treatment options for different subtypes of breast cancer.
Highlights
Breast cancer is the most common malignancy among women worldwide and the leading cause of female cancer-caused death
Patients with luminal A subtype tumors have a long-term risk of distant metastatic disease, which is attenuated by tamoxifen administration, whereas patients with luminal B subtype tumors have an early risk of distant metastatic disease, and tamoxifen benefits reduce over time [9]
Given the significance of eainsctlucdainngceerp. ithelial-to-mesenchymal transition (EMT) in tumor initiation and metastasis, effective therapeutic strategies and novel drugs targeting EMT in breast cancer have become critical for improving the survival rate and quality of life for those already diagnosed with cancer relapse
Summary
Breast cancer is the most common malignancy among women worldwide and the leading cause of female cancer-caused death. It is a heterogeneous disease with large variations in its prognosis, indicating its apparent genetic and histopathological disparity. Subjects diagnosed with the luminal B and HER2-enriched subtypes have a much lower survival rate and higher probability of relapse than those with the luminal A subtype. Given the significance of EMT in tumor initiation and metastasis, effective therapeutic strategies and novel drugs targeting EMT in breast cancer have become critical for improving the survival rate and quality of life for those already diagnosed with cancer relapse. Our findings could bridge the current gap in therapeutic intervention and management strategies for breast cancer in a setting of ethnic diversity
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