CCN2 and melanoma: It has also been shown that the exposure of melanoma cell lines to hypoxia up-regulated expression levels of HIF-1α and HIF-2α and their target genes including Oct-3/4, Nanog, Nodal, connective tissue growth factor (CTGF), snail-1 and VEGF that in turn promoted their self-renewal ability, tumourigenicity, metastatic potential and resistance to current chemotherapeutic drugs such as temozolomide and cisplatin as well as angiogenic switch [112, 170–172].