Rab31-dependent regulation of transforming growth factor ß expression in breast cancer cells

Background The small GTP-binding protein Rab31 plays an important role in the modulation of tumor biological-relevant processes, including cell proliferation, adhesion, and invasion. As an underlying mechanism, Rab31 is presumed to act as a molecular switch between a more proliferative and an invasi...

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Vydáno v:Molecular medicine (Cambridge, Mass.) Ročník 27; číslo 1; s. 158 - 17
Hlavní autoři: Soelch, Susanne, Beaufort, Nathalie, Loessner, Daniela, Kotzsch, Matthias, Reuning, Ute, Luther, Thomas, Kirchner, Thomas, Magdolen, Viktor
Médium: Journal Article
Jazyk:angličtina
Vydáno: London BioMed Central 14.12.2021
BMC
Témata:
Biomedical and Life Sciences
Biomedicine
Breast cancer
EMT
GTPase
Molecular Medicine
Rab31
Research Article
TGF-ß signaling
TGF-ß signaling
Rab31
Breast cancer
GTPase
EMT
ISSN:1076-1551, 1528-3658, 1528-3658
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Shrnutí:Background The small GTP-binding protein Rab31 plays an important role in the modulation of tumor biological-relevant processes, including cell proliferation, adhesion, and invasion. As an underlying mechanism, Rab31 is presumed to act as a molecular switch between a more proliferative and an invasive phenotype. This prompted us to analyze whether Rab31 overexpression in breast cancer cells affects expression of genes involved in epithelial-to-mesenchymal transition (EMT)-like processes when compared to Rab31 low-expressing cells. Methods Commercially available profiler PCR arrays were applied to search for differentially expressed genes in Rab31 high- and low-expressing CAMA-1 breast cancer cells. Differential expression of selected candidate genes in response to Rab31 overexpression in CAMA-1 cells was validated by independent qPCR and protein assays. Results Gene expression profiling of key genes involved in EMT, or its reciprocal process MET, identified 9 genes being significantly up- or down-regulated in Rab31 overexpressing CAMA-1 cells, with the strongest effects seen for TGFB1 , encoding TGF-ß1 (> 25-fold down-regulation in Rab31 overexpressing cells). Subsequent validation analyses by qPCR revealed a strong down-regulation of TGFB1 mRNA levels in response to increased Rab31 expression not only in CAMA-1 cells, but also in another breast cancer cell line, MDA-MB-231. Using ELISA and Western blot analysis, a considerable reduction of both intracellular and secreted TGF-ß1 antigen levels was determined in Rab31 overexpressing cells compared to vector control cells. Furthermore, reduced TGF-ß activity was observed upon Rab31 overexpression in CAMA-1 cells using a sensitive TGF-ß bioassay. Finally, the relationship between Rab31 expression and the TGF-ß axis was analyzed by another profiler PCR array focusing on genes involved in TGF-ß signaling. We found 12 out of 84 mRNAs significantly reduced and 7 mRNAs significantly increased upon Rab31 overexpression. Conclusions Our results demonstrate that Rab31 is a potent modulator of the expression of TGF-ß and other components of the TGF-ß signaling pathway in breast cancer cells.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1076-1551
1528-3658
1528-3658
DOI:10.1186/s10020-021-00419-8