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CRACD suppresses neuroendocrinal plasticity of lung adenocarcinoma

Tumor cell plasticity contributes to intratumoral heterogeneity and therapy resistance. Through cell plasticity, lung adenocarcinoma (LUAD) cells transform into neuroendocrinal (NE) tumor cells. However, the mechanisms of NE cell plasticity remain unclear. CRACD, a capping protein inhibitor, is freq...

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Autores principales: Kim, Bongjun, Zhang, Shengzhe, Huang, Yuanjian, Ko, Kyung-Pil, Zou, Gengyi, Zhang, Jie, Jun, Sohee, Kim, Kee-Beom, Jung, Youn-Sang, Park, Kwon-Sik, Park, Jae-Il
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10153265/
https://www.ncbi.nlm.nih.gov/pubmed/37131761
http://dx.doi.org/10.1101/2023.04.19.537576
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author Kim, Bongjun
Zhang, Shengzhe
Huang, Yuanjian
Ko, Kyung-Pil
Zou, Gengyi
Zhang, Jie
Jun, Sohee
Kim, Kee-Beom
Jung, Youn-Sang
Park, Kwon-Sik
Park, Jae-Il
author_facet Kim, Bongjun
Zhang, Shengzhe
Huang, Yuanjian
Ko, Kyung-Pil
Zou, Gengyi
Zhang, Jie
Jun, Sohee
Kim, Kee-Beom
Jung, Youn-Sang
Park, Kwon-Sik
Park, Jae-Il
author_sort Kim, Bongjun
collection PubMed
description Tumor cell plasticity contributes to intratumoral heterogeneity and therapy resistance. Through cell plasticity, lung adenocarcinoma (LUAD) cells transform into neuroendocrinal (NE) tumor cells. However, the mechanisms of NE cell plasticity remain unclear. CRACD, a capping protein inhibitor, is frequently inactivated in cancers. CRACD knock-out (KO) de-represses NE-related gene expression in the pulmonary epithelium and LUAD cells. In LUAD mouse models, Cracd KO increases intratumoral heterogeneity with NE gene expression. Single-cell transcriptomic analysis showed that Cracd KO-induced NE plasticity is associated with cell de-differentiation and activated stemness-related pathways. The single-cell transcriptomes of LUAD patient tumors recapitulate that the distinct LUAD NE cell cluster expressing NE genes is co-enriched with SOX2, OCT4, and NANOG pathway activation, and impaired actin remodeling. This study reveals an unexpected role of CRACD in restricting NE cell plasticity that induces cell de-differentiation, providing new insights into cell plasticity of LUAD.
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spelling pubmed-101532652023-05-03 CRACD suppresses neuroendocrinal plasticity of lung adenocarcinoma Kim, Bongjun Zhang, Shengzhe Huang, Yuanjian Ko, Kyung-Pil Zou, Gengyi Zhang, Jie Jun, Sohee Kim, Kee-Beom Jung, Youn-Sang Park, Kwon-Sik Park, Jae-Il bioRxiv Article Tumor cell plasticity contributes to intratumoral heterogeneity and therapy resistance. Through cell plasticity, lung adenocarcinoma (LUAD) cells transform into neuroendocrinal (NE) tumor cells. However, the mechanisms of NE cell plasticity remain unclear. CRACD, a capping protein inhibitor, is frequently inactivated in cancers. CRACD knock-out (KO) de-represses NE-related gene expression in the pulmonary epithelium and LUAD cells. In LUAD mouse models, Cracd KO increases intratumoral heterogeneity with NE gene expression. Single-cell transcriptomic analysis showed that Cracd KO-induced NE plasticity is associated with cell de-differentiation and activated stemness-related pathways. The single-cell transcriptomes of LUAD patient tumors recapitulate that the distinct LUAD NE cell cluster expressing NE genes is co-enriched with SOX2, OCT4, and NANOG pathway activation, and impaired actin remodeling. This study reveals an unexpected role of CRACD in restricting NE cell plasticity that induces cell de-differentiation, providing new insights into cell plasticity of LUAD. Cold Spring Harbor Laboratory 2023-04-21 /pmc/articles/PMC10153265/ /pubmed/37131761 http://dx.doi.org/10.1101/2023.04.19.537576 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Kim, Bongjun
Zhang, Shengzhe
Huang, Yuanjian
Ko, Kyung-Pil
Zou, Gengyi
Zhang, Jie
Jun, Sohee
Kim, Kee-Beom
Jung, Youn-Sang
Park, Kwon-Sik
Park, Jae-Il
CRACD suppresses neuroendocrinal plasticity of lung adenocarcinoma
title CRACD suppresses neuroendocrinal plasticity of lung adenocarcinoma
title_full CRACD suppresses neuroendocrinal plasticity of lung adenocarcinoma
title_fullStr CRACD suppresses neuroendocrinal plasticity of lung adenocarcinoma
title_full_unstemmed CRACD suppresses neuroendocrinal plasticity of lung adenocarcinoma
title_short CRACD suppresses neuroendocrinal plasticity of lung adenocarcinoma
title_sort cracd suppresses neuroendocrinal plasticity of lung adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10153265/
https://www.ncbi.nlm.nih.gov/pubmed/37131761
http://dx.doi.org/10.1101/2023.04.19.537576
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