Figure 1. Cancer stem cell and their overexpressed markers.
In cancer metastasis, generally five steps are described: invasion, intravasation, transport, extravasation, and colonization (Tsai & Yang, 2013) . EMT is vital for intravasation and extravasation. However, a loss of EMT induction signaling is necessary to achieve proliferation of cancer cells. This process of EMT reversal, called mesenchymal-epithelial transition (MET) that helps in tumor growth(Chang, 2016; Tsai & Yang, 2013) . As an outcome of the whole transition process, the tumor cells become more invasive, metastasize and depict resistance to chemotherapy and radiotherapy (Naveen et al., 2016) .
Regulation of CSCs is brought about by several different mechanisms such as Janus-activated kinase/signal transducer and activator of transcription (JAK/STAT), nuclear factor-kappa B (NF-κB), phosphatidylinositol 3-kinase-Akt (PI3K-Akt), Hedgehog, Wnt, and Notch signaling pathways that are discussed below and have shown to mediate the stemness of CSCs as shown in Figure 2 (Gupta et al., 2020, Matsui, 2016) .