@article{10902/34535,
year = {2024},
url = {https://hdl.handle.net/10902/34535},
abstract = {Squamous or epidermoid cancer arises in stratified epithelia but also is frequent in the non-epidermoid epithelium of the lung by unclear mechanisms. A poorly studied mitotic checkpoint drives epithelial cells bearing irreparable genetic damage into epidermoid differentiation. We performed an RNA-sequencing gene search to target unknown regulators of this response and selected the SUMO regulatory protein SENP2. Alterations of SENP2 expression have been associated with some types of cancer. We found the protein to be strongly localised to mitotic spindles of freshly isolated human epidermal cells. Primary cells rapidly differentiated after silencing SENP2 with specific shRNAs. Loss of SENP2 produced in synchronised epithelial cells delays in mitotic entry and exit and defects in chromosomal alignment. The results altogether strongly argue for an essential role of SENP2 in the mitotic spindle and hence in controlling differentiation. In addition, the expression of SENP2 displayed an inverse correlation with the immuno-checkpoint biomarker PD-L1 in a pilot collection of aggressive lung carcinomas. Consistently, metastatic head and neck cancer cells that do not respond to the mitosis-differentiation checkpoint were resistant to depletion of SENP2. Our results identify SENP2 as a novel regulator of the epithelial mitosis-differentiation checkpoint and a potential biomarker in epithelial cancer.},
organization = {Acknowledgements: we thank Stefan Stoll and Ignacio Varela for advice, Darío Alves, Rajan Nair and Nerea Martínez for technical assistance and Fe García-Reija for head and neck biopsies. This work was funded by Instituto de Salud Carlos III (ISCIII)-FEDER, grants PI14/00900, PI17/03107 and PI20/00880 (AG; Spain), National Institutes of Health (NIH) grant R01-AR052889 (JTE, USA) and CRUK program grant C28206/A14499 (HH, UK). JG was recipient of a predoctoral scholarship from Asociación Española Contra el Cáncer (AECC; Spain), PRDCA19003GALA; and a scientific exchange grant from EMBO, SEG9382. RM was recipient of a scientific exchange grant from EMBO, ASTF 226-2016.},
publisher = {Nature Publishing Group},
publisher = {Cell Death and Disease, 2024, 15, 596},
title = {Sumo-regulatory SENP2 controls the homeostatic squamous mitosis-differentiation checkpoint},
author = {Galán-Vidal, Jesús and García Gaipo, Lorena and Molinuevo, Rut and Dias, Samantha and Tsoi, Alex and Gómez Román, José Javier and Elder, James T. and Hochegger, Helfrid and Gandarillas Solinis, Alberto},
}