Characterizing the Relapse Potential in Different Luminal Subtypes of Breast Cancers with Functional Proteomics

Tung Yi Lin, Pei Wen Wang, Chun Hsun Huang, Pei Ming Yang, Tai Long Pan

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number6077
Pages (from-to)1-16
Number of pages16
JournalInternational journal of molecular sciences
Volume21
Issue number17
DOIs
Publication statusPublished - Sep 1 2020

Keywords

  • breast cancer
  • estrogen receptor
  • human epidermal growth factor receptor 2
  • luminal B subtype
  • network analysis
  • proteomics
  • Estrogen receptor
  • Human epidermal growth factor receptor 2
  • Network analysis
  • Proteomics
  • Breast cancer
  • Luminal B subtype

ASJC Scopus subject areas

  • Molecular Biology
  • Spectroscopy
  • Catalysis
  • Inorganic Chemistry
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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