DNMT3a-dermatopontin axis suppresses breast cancer malignancy via inactivating YAP

Danrong Ye1, Yuying Wang1, Xiaochong Deng2

  • 1Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.

Cell Death & Disease
|February 11, 2023
PubMed

Insights

Dermatopontin (DPT) downregulation, caused by DNA methylation, worsens breast cancer (BC) prognosis. DPT inhibits BC growth and metastasis by interacting with YAP, suggesting DPT/YAP modulation as a potential therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Breast cancer (BC) is a leading cause of cancer mortality in women globally.
  • Tumorigenesis and progression mechanisms in BC require further elucidation.
  • Dermatopontin (DPT), an extracellular matrix protein, is implicated in cancer development.

Purpose of the Study:

  • To investigate the role of dermatopontin (DPT) in breast cancer (BC) progression.
  • To elucidate the regulatory mechanisms of DPT expression in BC.
  • To explore the interaction between DPT and YAP in BC pathogenesis.

Main Methods:

  • Analysis of DPT promoter hypermethylation mediated by DNMT3a.
  • Correlation of DPT expression levels with patient prognosis.
  • Investigation of DPT's interaction with YAP and its effect on YAP translocation.
  • Assessment of YAP overexpression effects on BC cell growth and metastasis.

Main Results:

  • DNMT3a-mediated DPT promoter hypermethylation leads to DPT downregulation in BC.
  • Low DPT expression correlates significantly with poor BC prognosis.
  • DPT interacts with YAP, promoting YAP phosphorylation and inhibiting its nuclear translocation.
  • Ectopic YAP overexpression counteracts DPT's inhibitory effects on BC growth and metastasis.

Conclusions:

  • DPT plays a critical role in suppressing malignant phenotypes in breast cancer.
  • DPT functions by inhibiting YAP nuclear translocation, thereby controlling BC progression.
  • Modulating the DPT/YAP pathway presents a potential therapeutic strategy for breast cancer.

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