Inhibition of Nuclear Pore Complex Formation Selectively Induces Cancer Cell Death.

Inhibition of Nuclear Pore Complex Formation Selectively Induces Cancer Cell Death.:

Inhibition of Nuclear Pore Complex Formation Selectively Induces Cancer Cell Death.

Cancer Discov. 2020 Sep 28;:

Authors: Sakuma S, Raices M, Borlido J, Guglielmi V, Zhu EYS, D'Angelo MA

Abstract

Nuclear pore complexes (NPCs) are the central mediators of nucleocytoplasmic transport. Increasing evidence shows that many cancer cells have increased numbers of NPCs and become addicted to the nuclear transport machinery. How reducing NPC numbers affects the physiology of normal and cancer cells and if it could be exploited for cancer therapies has not been investigated. We report that inhibition of NPC formation, a process mostly restricted to proliferating cells, causes selective cancer cell death, prevents tumor growth and induces tumor regression. While cancer cells die in response to NPC assembly inhibition, normal cells undergo a reversible cell cycle arrest that allows them to survive. Mechanistically, reducing NPC numbers results in multiple alterations contributing to cancer cell death including abnormalities in nuclear transport, catastrophic alterations in gene expression, and the selective accumulation of DNA damage. Our findings uncover the NPC formation process as a novel targetable pathway in cancer cells.



PMID: 32988961 [PubMed - as supplied by publisher]