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Updated: Jan 30, 2026

Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
Published on: May 17, 2019
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.
Abstract:
Protein Kinase D (PKD) family contains PKD1, PKD2, and PKD3 in human. Compared to consistent tumor-suppressive functions of PKD1 in breast cancer, how PKD2/3 functions in breast cancer are not fully understood. In the current study, we found that PKD2 and PKD3 but not PKD1 were preferentially overexpressed in breast cancer and involved in regulating cell proliferation and metastasis. Integrated phosphoproteome, transcriptome, and interactome showed that PKD2 was associated with multiple cancer-related pathways, including adherent junction, regulation of actin cytoskeleton, and cell cycle-related pathways. ELAVL1 was identified as a common hub-node in networks of PKD2/3-regulated phosphoproteins and genes. Silencing ELAVL1 inhibited breast cancer growth in vitro and in vivo. Direct interaction between ELAVL1 and PKD2 or PKD3 was demonstrated. Suppression of PKD2 led to ELAVL1 translocation from the cytoplasm to the nucleus without significant affecting ELAVL1 expression. Taken together, we characterized the oncogenic functions of PKD2/3 in breast cancer and their association with cancer-related pathways, which shed lights on the oncogenic roles and mechanisms of PKDs in breast cancer.
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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