High-Speed Atomic Force Microscopy Reveals Loss of Nuclear Pore Resilience as a Dying Code in Colorectal Cancer Cells

ACS Nano
Mahmoud Shaaban MohamedRichard W Wong

Abstract

Nuclear pore complexes (NPCs) are the sole turnstile implanted in the nuclear envelope (NE), acting as a central nanoregulator of transport between the cytosol and the nucleus. NPCs consist of ∼30 proteins, termed nucleoporins. About one-third of nucleoporins harbor natively unstructured, intrinsically disordered phenylalanine-glycine strings (FG-Nups), which engage in transport selectivity. Because the barriers insert deeply in the NPC, they are nearly inaccessible. Several in vitro barrier models have been proposed; however, the dynamic FG-Nups protein molecules themselves are imperceptible in vivo. We show here that high-speed atomic force microscopy (HS-AFM) can be used to directly visualize nanotopographical changes of the nuclear pore inner channel in colorectal cancer (CRC) cells. Furthermore, using MLN8237/alisertib, an apoptotic and autophagic inducer currently being tested in relapsed cancer clinical trials, we unveiled the functional loss of nucleoporins, particularly the deformation of the FG-Nups barrier, in dying cancer cells. We propose that the loss of this nanoscopic resilience is an irreversible dying code in cells. These findings not only illuminate the potential application of HS-AFM as an intracellular nano...Continue Reading

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Citations

Oct 28, 2019·Journal of Cancer Research and Clinical Oncology·Adhiraj Roy, Gopeshwar Narayan
Jul 10, 2020·Chemical Communications : Chem Comm·Nesreen HamadMasato Katahira
Nov 21, 2018·Life Science Alliance·George J StanleyBart W Hoogenboom
Dec 13, 2018·Journal of Nanobiotechnology·Xiangying DengZhaoyang Zeng
Aug 8, 2019·Cell Division· HartonoRichard W Wong
Dec 29, 2020·Biochemical and Biophysical Research Communications·Koki KatoRichard W Wong
Jun 30, 2019·Current Opinion in Chemical Biology·Toshio Ando
Apr 15, 2021·The Journal of Physical Chemistry Letters·Goro NishideRichard W Wong
Jul 30, 2021·Frontiers in Cell and Developmental Biology·Yoichi ShinkaiTakamitsu Miyafusa
Aug 28, 2021·Cells·Richard W Wong

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