Oncogenic functions of protein kinase D2 and D3 in regulating multiple cancer-related pathways in breast cancer

Yan Liu1,2,3,4, Jian Li2, Zhifang Ma1

  • 1Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China.

Cancer Medicine
|January 18, 2019
PubMed

Insights

Protein Kinase D (PKD) 2 and 3 are overexpressed in breast cancer, promoting cell growth and metastasis. These kinases interact with ELAVL1, a key regulator, offering potential therapeutic targets for breast cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The Protein Kinase D (PKD) family, including PKD1, PKD2, and PKD3, plays diverse roles in cellular processes.
  • While PKD1 is known for tumor suppression in breast cancer, the functions of PKD2 and PKD3 remain less understood.

Purpose of the Study:

  • To investigate the roles and mechanisms of PKD2 and PKD3 in breast cancer.
  • To identify key molecular players and pathways associated with PKD2/3 in breast cancer progression.

Main Methods:

  • Comparative analysis of PKD family members' expression in breast cancer.
  • Integrated phosphoproteome, transcriptome, and interactome analyses.
  • In vitro and in vivo functional assays, including gene silencing and protein interaction studies.

Main Results:

  • PKD2 and PKD3 are significantly overexpressed in breast cancer, unlike PKD1.
  • PKD2/3 regulate cell proliferation and metastasis, associating with pathways like adherent junction and cell cycle.
  • ELAVL1 was identified as a crucial hub node interacting with PKD2/3, and its silencing inhibited tumor growth.

Conclusions:

  • PKD2 and PKD3 exhibit oncogenic functions in breast cancer by regulating critical cellular pathways.
  • The interaction between PKD2/3 and ELAVL1 highlights a novel mechanism in breast cancer development.
  • Targeting PKD2/3 or ELAVL1 may offer new therapeutic strategies for breast cancer.

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