Gil and colleagues first identified CBX7 and found that the lifespan of differentiated human cells was extended and the immortalization of mouse fibroblasts was established via increased CBX7 levels which was followed by downregulating expression of the Ink4a/Arf locus [1, 2]. CBX7 also cooperated with c-Myc and initiated lymphomagenesis . However, of note, CBX7 expression has a negative correlation with advanced tumor aggressiveness and poor prognosis in a wide range of tumor types, such as thyroid, colorectal, pancreas, breast, lung, and glioblastoma (GBM) [9–18]. The contradictory behavior of CBX7 in different kinds of tumors reflects the notion that cellular context plays an essential role in the effects of the CBX7.