Of gastriccancer cells. This increase in apoptosis could well be explained by the observed increase of p53 expression in GTSE1 knocked-down cells. P53 is a potent inhibitor of cell growth and its function is tightly controlled to allow normal growth development [31]. In response to DNA damage insults, p53 induces cell cycle arrest and activates the intrinsic apoptotic signaling pathway [32]. P53 up regulation also resulted in activation of its downstream effectors- bax. This could attribute to chromatin condensation, DNA fragmentation and finally apoptosis [33]. Hence, up regulation of p53 and its downstream effectors in cisplatin treated cells can be inferred PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27527552 as a cellular response to DNA damage. Therefore, by identifying a reduced expression profile of p53 in normal cells against GTSE1 knocked-down cells, our study demonstrates a role of GTSE1 in attenuating p53 mediated apoptotic response in cisplatin treated gastric cancer cells. However, we did not see any significant difference in caspase 3 activation in GTSE1 knock down cells upon cisplatin treatment, as compared to its parental counterparts (Additional file 1: Figure S4). Our findings suggest that GTSE1 mediates a caspase 3 independent cascade of apoptotic repression in cisplatin treated gastric cancer cells. This is consistent with previous studies by and Cui et al. and Hu et al. that have shown a p53 dependent but caspase 3 independent mechanism of apoptosis [34, 35]. In addition, GTSE1 expression was also seen to be associated with high expression of p21 as knockdown of GTSE1 caused a reduction in p21 turn over. This falls in agreement with studies by Bublik et al. that showed GTSE1 as a regulator of p21 stability by protecting it from proteosome-dependent degradationEarlier, the association of GTSE1 with p21 was shown to modulate cellular response to paclitaxel induced apoptosis in cervical cancer cells [36]. Moreover, high levels of p21 in cancers have been linked to poor prognosis [37]. Thus, by oppositely regulating p53 and p21, GTSE1 protein may display a combined role in promoting cell survival by shifting the equilibrium of p53 response from apoptosis to survival [23]. Hence, targeting GTSE1 in cancer therapy could enhance a p53 mediated pro-apoptotic response with a reflective decrease in p21 induced cell cycle arrest.Conclusion Individualisation of therapy according to the molecular phenotype of tumour and patient could dramatically increase the effectiveness of chemotherapy. The study presented here BMS-986020 molecular weight emphasizes the predictive value of GTSESubhash et al. BMC Cancer (2015) 15:Page 11 ofas a biomarker for cisplatin resistance in gastric cancer. Although previous studies in lung cancer patients did not show any correlation of GTSE1 with clinical data, the drug sensitivity profile and down-regulation of p53 induced apoptotic signaling in GTSE1 knocked-down gastric cancer cells is intriguing and warrants an in depth analysis of its clinical significance. Future studies should utilize animal models to further explore the therapeutic utility of GTSE1 in gastric cancer. Nevertheless, our study identifies a previously uncharacterized role of GTSE1 in conferring cisplatin resistance and presents an additional avenue for future therapeutic intervention and patient stratification in gastric cancer.5.6.7. 8.9. 10. 11.Additional fileAdditional file 1: Table S1. Surgical results. Figure S1. Radiological response after 2 cycles of chemotherapy (n = 17). Figure S2. GTSE1 methylation.