Biology subjects

Kropyvko, S.

Publications and source records attributed to Kropyvko, S..

3 recordsLinked to original sources

bioRxiv2026

Differential Expression of TKS4 Isoforms and Their Role in Cellular Processes in Breast Cancer

The scaffold protein TKS4 plays a role in the development of several cancers. Alternative splicing of the TKS4 gene generates two isoforms, TKS4L and TKS4b; however, their distinct expression patterns and functional roles have not yet been characterized. We have shown that TKS4 isoforms were differentially expressed across human cell lines and breast cancer (BC) tumor samples. Both TKS4L and TKS4L/TKS4b mRNA ratios were significantly altered in tumors compared with adjacent tissues. We identified six novel binding SH3-domain-containing partners for TKS4L, none of which interact with TKS4b, suggesting their functional differences. Tyrosine phosphorylation of both isoforms was induced by Src(Y527F) kinase overexpression, enabling binding to the SH2 domains of signaling proteins. Interestingly, TKS4b significantly accumulated in the nucleus, while TKS4L was primarily present in the cytosol in MCF-7 cells. TKS4b overexpression enhanced MCF-7 cell migration. Both TKS4 isoforms exhibit oncogenic properties by promoting epithelial-mesenchymal transition in BC cells, highlighting their potential as targets for therapeutic intervention.

molecular biology↗

bioRxiv2022

Tristetraproline in breast cancer: treat or trick?

Breast cancer is one of the most common types of cancer. It is very heterogeneous, hence still complicated to diagnose despite of decades of research. Post-transcriptional regulation of gene expression is crucial for modulation of cell networking and is performed via different regulatory molecules. Tristetraproline (TTP) is RNA-binding protein which binds to AU-rich elements within its target mRNAs and negatively regulates multiple transcripts, including pro-inflammatory and pro-oncogenic. Its expression level correlates with patient outcomes in different types of cancer and is considered as a potential molecular marker. Here we examined TTPs expression level in different molecular subtypes of breast cancer. Our findings show that TTP expression is significantly higher in HER2-enriched breast cancer compared to other types and adjacent tissues. We also investigated changes in the TTPs methylation status under temozolomide and doxorubicin treatment in MCF-7 cell line and found that temozolomide decreased TTPs methylation, which can potentially improve patient prognosis. In contrast, another well-known anticancer agent, doxorubicin, promoted TTPs methylation, which may impair an expected therapeutic effect of this drug.

cancer biology↗

bioRxiv2019

The atypical Rho GTPase RhoU interacts with Intersectin-2 to regulate endosomal recycling pathways

Rho GTPases play a key role in various membrane trafficking processes. RhoU is an atypical small Rho GTPase related to Rac/Cdc42 which possesses unique N- and C-terminal domains that regulate its function and its subcellular localization. RhoU localized at the plasma membrane, on endosomes and in cell adhesion structures where it governs cell signalling, differentiation and migration. However, despite its endomembrane localization, RhoU function in vesicular trafficking has been unexplored. Here, we identified intersectins (ITSNs) as new binding partners for RhoU and showed that the second PxxP motif at the N-terminus of RhoU mediated interactions with SH3 domains of ITSNs. To evaluate the function of RhoU and ITSNs in vesicular trafficking, we used fluorescent transferrin as a cargo for uptake experiments. We showed that silencing of either RhoU or ITSN2, but not ITSN1 increased transferrin accumulation in early endosomes resulting from defect in fast vesicle recycling. Concomitantly, RhoU and ITSN2 colocalized to a subset of Rab4-positive vesicles suggesting that RhoU-ITSN2 interaction may occur on fast recycling endosomes to regulate the fate of vesicular cargos.

cell biology↗