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HOXB13 interactome in prostate cancer cells: biochemical and functional interactions between the transcription
М M Erokhin1, N Y Kozelchuk1, R H Ziganshin2
1Institute of Gene Biology of the Russian Academy of Sciences, Moscow, Russia.
Abstract:
Transcription factors represent one of the major groups of proteins, whose suppression leads to tumor growth arrest. Different types of cancer express a specific set of transcription factors that create and maintain unique patterns of gene expression. In prostate cancer cells, one of the key transcriptional regulators is the HOXB13 (Homeobox B13) protein. HOXB13 is known to be an important regulator of embryonic development and terminal cell differentiation. HOXB13 regulates the transcription of many genes in normal and transformed prostate cells and is also capable of acting as a pioneer factor that opens chromatin in the regulatory regions of genes. However, little is known about the protein partners and functions of HOXB13 in prostate cells. In the present study, we searched for protein partners of HOXB13 by immunoaffinity purification followed by high-throughput mass spectrometric analysis (IP/LC-MS) using the PC-3 prostate cancer cell line as a model. The main partners of HOXB13 were found to be transcription factors with different types of DNA-binding domains, including the TBX3, TBX2, ZFHX4, ZFHX3, RUNX1, NFAT5 proteins. Using the DepMap resource, we have shown that one of the identified partners, the TBX3 protein is as critical for the growth and proliferation of prostate cancer cell lines in vitro as HOXB13. Analysis of individual prostate cancer cell lines revealed that knockout of both genes, HOXB13 and TBX3, leads to the death of the same lines: VCaP, LNCaP (clone FGC), PC-3 and 22Rv1. Thus, HOXB13 and TBX3 can be considered together as potential targets for the development of specific inhibitors that suppress prostate cancer cell growth.
Insights
Homeobox B13 (HOXB13) and TBX3 are key transcription factors in prostate cancer. Targeting both HOXB13 and TBX3 may inhibit prostate cancer cell growth, offering new therapeutic strategies.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Transcription factors regulate gene expression crucial for cell function.
- HOXB13 is a key regulator in prostate cells, influencing development and differentiation.
- Understanding HOXB13's protein interactions is vital for prostate cancer research.
Purpose of the Study:
- To identify protein partners of HOXB13 in prostate cancer cells.
- To investigate the functional significance of HOXB13 interactions.
- To explore potential therapeutic targets for prostate cancer.
Main Methods:
- Immunoaffinity purification followed by liquid chromatography-mass spectrometry (IP/LC-MS) was used to identify HOXB13 partners.
- Prostate cancer cell lines (PC-3) were utilized as a model system.
- DepMap resource was used to assess gene dependency.
Main Results:
- Several transcription factors, including TBX3, TBX2, ZFHX4, ZFHX3, RUNX1, and NFAT5, were identified as HOXB13 partners.
- TBX3 was found to be critical for prostate cancer cell line growth and proliferation, similar to HOXB13.
- Simultaneous knockout of HOXB13 and TBX3 resulted in cell death across multiple prostate cancer lines (VCaP, LNCaP, PC-3, 22Rv1).
Conclusions:
- HOXB13 interacts with multiple transcription factors, notably TBX3, in prostate cancer cells.
- Combined targeting of HOXB13 and TBX3 presents a promising strategy for inhibiting prostate cancer growth.
- These findings suggest HOXB13 and TBX3 as potential therapeutic targets for novel prostate cancer treatments.
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