Hexavalent chromium causes centrosome amplification by inhibiting the binding between TMOD2 and NPM2

Abstract

Background: Hexavalent chromium can promote centrosome amplification (CA) as well as tumorigenesis. Since CA can lead to tumorigenesis, it is plausible that the chromium promotes the development of cancer via CA. In the present study, we investigated the signaling pathways of the chromium-induced CA.

Results: Our results showed that sub-toxic concentration of chromium was able to cause CA in HCT116 cells, and decrease the expression of TMOD2 and NPM2. Furthermore, TMOD2 and NPM2 interacted to each other via their C-terminal and the N-terminal, respectively, which was inhibited by the chromium. Overexpression of TMOD2 and NPM2 increased their binding and significantly attenuated the CA. Moreover, TMOD2 and NPM2 were co-localized with the centrosomes. The chromium inhibited the centrosomeal localization of NPM2, which was reversed by the overexpression of TMOD2, C-terminal of TMOD2, but not the N-terminal of NPM2.

Conclusion: Our results suggest that the chromium induces CA via inhibiting the binding between TMOD2 and NPM2 as well as the dissociation of NPM2 from centrosomes.

Keywords: Centrosomal localization; Centrosome amplification; Hexavalent chromium; NPM2; Protein-protein binding; TMOD2.