Somatic-to-primordial Germ Cell-Like Transformation is Critical in Tumor Initiation of Mouse Breast Tumor 4T1 Cells.

It has been proposed that tumorigenicity was an intrinsic feature of embryonic/germ cell developmental axis as well as embryonic/germ cell-related genes play a crucial role in tumorigenicity. Our previous studies indicated that primordial germ cell (PGC)-like potential could be reactivated in tumorigenesis. In this study, 4T1, 168FARN and 67NR cells which originated from the same mouse breast cancer were studied and the results indicated that the acquisition of embryonic/germ cell-like state is essential for tumorigenicity. We further demonstrated that somatic to PGC-like transformation (SPLT) was activated in 4T1 cells and that inhibition of PGC-like cell formation by depleting pluripotency and/or PGC specification-related genes markedly repressed SPLT and the tumorigenicity. Collectively, our findings reveal that tumorigenicity is linked to the acquisition of PGC-like state through SPLT in 4T1 cells, providing new insight into deeper understanding the biological nature of tumors and novel therapeutical strategies for cancer targeting.