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Updated: Mar 7, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
The tumor suppressor RhoBTB1 controls Golgi integrity and breast cancer cell invasion through METTL7B
Caroline M McKinnon1, Harry Mellor2
1School of Biochemistry, Biomedical Sciences Building, University Walk, University of Bristol, Bristol, UK.
Background:
RhoBTB1 and 2 are atypical members of the Rho GTPase family of signaling proteins. Unlike other Rho GTPases, RhoBTB1 and 2 undergo silencing or mutation in a wide range of epithelial cancers; however, little is known about the consequences of this loss of function.
Methods:
We analyzed transcriptome data to identify transcriptional targets of RhoBTB2. We verified these using Q-PCR and then used gene silencing and cell imaging to determine the cellular function of these targets downstream of RhoBTB signaling.
Results:
RhoBTB1 and 2 regulate the expression of the methyltransferases METTL7B and METTL7A, respectively. RhoBTB1 regulates the integrity of the Golgi complex through METTL7B. RhoBTB1 is required for expression of METTL7B and silencing of either protein leads to fragmentation of the Golgi. Loss of RhoBTB1 expression is linked to Golgi fragmentation in breast cancer cells. Restoration of normal RhoBTB1 expression rescues Golgi morphology and dramatically inhibits breast cancer cell invasion.
Conclusion:
Loss of RhoBTB1 expression in breast cancer cells leads to Golgi fragmentation and hence loss of normal polarity.
Insights
Loss of RhoBTB1, a Rho GTPase, causes Golgi fragmentation in breast cancer cells. Restoring RhoBTB1 expression inhibits cancer cell invasion, highlighting its role in cell polarity and integrity.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- RhoBTB1 and 2 are atypical Rho GTPases implicated in various epithelial cancers.
- Their loss of function in cancer is poorly understood.
- Investigating RhoBTB1/2 function is crucial for understanding cancer progression.
Purpose of the Study:
- Identify transcriptional targets of RhoBTB2.
- Determine the cellular functions regulated by RhoBTB signaling.
- Elucidate the role of RhoBTB1 in breast cancer.
Main Methods:
- Transcriptome data analysis to identify RhoBTB2 targets.
- Quantitative PCR (Q-PCR) for target verification.
- Gene silencing and cell imaging for functional analysis.
Main Results:
- RhoBTB1 and 2 regulate methyltransferases METTL7B and METTL7A, respectively.
- RhoBTB1 controls Golgi complex integrity via METTL7B.
- Loss of RhoBTB1 leads to Golgi fragmentation, observed in breast cancer cells.
- Restoring RhoBTB1 expression reverses Golgi fragmentation and inhibits invasion.
Conclusions:
- RhoBTB1 loss in breast cancer causes Golgi fragmentation and polarity loss.
- RhoBTB1 plays a critical role in maintaining Golgi integrity and cell polarity.
- Targeting RhoBTB1 may offer therapeutic strategies for breast cancer.
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