Abstract
It has been increasingly recognized that SNAIL1 and SNAIL2, as major EMT-inducers, might also be involved in drug resistance of cancer cells. We sought to determine a relation between SNAIL1/2, E-cadherin and N-cadherin expression, as well as ovarian cancer cells’ resistance to cisplatin and EMT markers’ level. Thus, four ovarian cancer cell lines, were used: A2780, A2780cis, SK-OV-3 and OVCAR-3. We assessed the impact of ERK1/2, AKT and STAT3 proteins (chosen by the profiling activity of over 40 signaling proteins) on SNAIL1/2 expression, along with E-cadherin and N-cadherin levels. We showed that expression of SNAIL1 and N-cadherin are the highest in cisplatin-resistant A2780cis and SK-OV-3 cells, while high SNAIL2 and E-cadherin levels were observed in cisplatin-sensitive A2780 cells. The highest E-cadherin level was noticed in OVCAR-3 cells. SNAIL1/2 expression was dependent on ERK1/2 activity in cisplatin-resistant and potentially invasive SK-OV-3 and OVCAR-3 cells. STAT-3 regulates expression of SNAIL1/2 and leads to the so-called “cadherin switch” in cancer cells, independently of their chemoresistance. In conclusion, SNAIL1, but not SNAIL2, seems to be involved in ovarian cancer cells’ cisplatin resistance. STAT3 is a universal factor determining the expression of SNAIL1/2 in ovarian cancer cells regardless of their chemoresitance or invasive capabilities.
Highlights
The accepted standard of the first-line chemotherapy of epithelial ovarian cancer (EOC) covers the combination of a platinum-containing agent and a member of taxanes
Metastatic sites differ from primary tumor in response to chemotherapeutic agents, as invading cancer cells are characterized by enhanced chemoresistance, which further limits the effectiveness of treatment [4]
The epithelial to mesenchymal transition (EMT) process is determined by a complex network of transcription factors, among which, those belonging to the SNAIL family (SNAIL 1, 2, 3), basic helix–loop–helix family (TWIST 1 and TWIST 2) and zinc-finger E-box-binding homeobox family (ZEB 1 and ZEB 2) seem to have the leading roles
Summary
The accepted standard of the first-line chemotherapy of epithelial ovarian cancer (EOC) covers the combination of a platinum-containing agent (cisplatin, carboplatin) and a member of taxanes (paclitaxel, docetaxel). Since the majority of malignant tumors are of epithelial origin, the ability to change their morphology and phenotype is required in order to disseminate from primary tumor and invade distant sites in organism In this regard, the epithelial to mesenchymal transition (EMT) process is absolutely essential and a key part of the metastatic cascade event. The EMT process is determined by a complex network of transcription factors, among which, those belonging to the SNAIL family (SNAIL 1, 2, 3), basic helix–loop–helix (bHLH) family (TWIST 1 and TWIST 2) and zinc-finger E-box-binding homeobox family (ZEB 1 and ZEB 2) seem to have the leading roles They are often termed “master regulators” of EMT, since their activity leads to the downregulation of epithelial genes and upregulation of genes associated with mesenchymal phenotype [6,7]. The exact molecular mechanisms responsible for the induction of both phenomena in ovarian cancer cells have not been clarified
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.