Fig. 6

Proposed model of cisplatin induced CSC enrichment during cisplatin resistance. In platinum resistant cells, cisplatin mediated NF-κB activation only in cancer stem cells, which in turn activates bimodal feedback loop of NF-κB-TNFα and NF-κB-PIK3CA. In one hand, it promotes an autocrine loop by activating TNFα-NF-κB in CSC’c, and on another hand, it increases PIK3CA and PI3K/AKT signalling thus leading to NF-κB stabilisation. Activated PI3K/AKT confers resistance against cisplatin action through modulation of anti-apoptotic (increase in cFLIP) and pro-apoptotic (decrease in BAX and PUMA) genes. A constant supply of NF-κB through TNFα-NF-κB autocrine loop and enhanced stabilisation of NF-κB by activated AKT maintains an anti-apoptotic, quiescent CSC state confers their survival against chemotherapeutics in resistant cells