In the present study, we report (i) the generation of a 17-kDa cleaved MUC16 (MUC16-Cter) using dual-epitope tagged 114 amino acids of carboxyl-terminal MUC16 in PC cells, (ii) MUC16-Cter mediated enrichment of ALDH+ cancer stem-like cells imparts tumorigenic, metastatic and drug resistant properties to PC cells and (iii) MUC16-Cter mediated enrichment of stemness specific genes LMO2 and NANOG is dependent on nuclear JAK2. Here, LMO2 is linked to pachyonychia congenita.