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PRDM4 mediates YAP-induced cell invasion by activating leukocyte-specific integrin β2 expression
Huan Liu1, Xiaoming Dai1, Xiaolei Cao1
1Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, China.
EMBO Reports
|April 20, 2018
Summary
Yes-associated protein (YAP) drives cancer cell invasion by inducing leukocyte integrin expression. PR/SET domain 4 (PRDM4) mediates this process, offering potential therapeutic targets for metastatic prostate cancer.
Area of Science:
- Cell Biology
- Molecular Oncology
- Cancer Metastasis Research
Background:
- Yes-associated protein (YAP) is a key Hippo pathway effector promoting cell proliferation and stemness.
- YAP deregulation is implicated in cancer initiation and progression, but its role in metastasis is unclear.
Purpose of the Study:
- To elucidate the mechanisms by which YAP promotes cancer cell invasion and metastasis.
- To identify novel YAP targets and regulators involved in cancer cell motility.
Main Methods:
- Biochemical purification and functional screening to identify YAP-interacting proteins.
- Analysis of integrin beta 2 (ITGB2) and PR/SET domain 4 (PRDM4) expression in cancer cells and patient samples.
- Investigating the role of YAP, ITGB2, and PRDM4 in endothelial invasion and tumorigenesis.
Main Results:
- YAP induces leukocyte-specific integrin beta 2 (ITGB2) expression in cancer cells, enhancing endothelial invasion.
- PR/SET domain 4 (PRDM4) was identified as a transcription factor interacting with YAP to mediate ITGB2 expression and invasion.
- Elevated ITGB2 and PRDM4 mRNA levels correlate with metastatic prostate cancer, and PRDM4 contributes to YAP-driven tumorigenesis.
Conclusions:
- YAP promotes cancer cell invasion by inducing leukocyte-specific integrin expression, mimicking leukocyte motility.
- PRDM4 is a novel YAP target gene and transcription factor crucial for YAP-mediated invasion and potentially tumorigenesis.
- Targeting the YAP-PRDM4-ITGB2 axis may offer new strategies against metastatic cancer.
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