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CRACD loss induces neuroendocrine cell plasticity of lung adenocarcinoma.
Kim, Bongjun; Zhang, Shengzhe; Huang, Yuanjian; Ko, Kyung-Pil; Jung, Youn-Sang; Jang, Jinho; Zou, Gengyi; Zhang, Jie; Jun, Sohee; Kim, Kee-Beom; Park, Kwon-Sik; Park, Jae-Il.
Afiliación
  • Kim B; Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: bkim6@mdanderseon.org.
  • Zhang S; Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Huang Y; Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Ko KP; Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Jung YS; Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Jang J; Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Zou G; Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Zhang J; Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Jun S; Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Kim KB; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; BK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.
  • Park KS; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
  • Park JI; Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Program in Genetics and Epigene
Cell Rep ; 43(6): 114286, 2024 Jun 25.
Article en En | MEDLINE | ID: mdl-38796854
ABSTRACT
Tumor cell plasticity contributes to intratumoral heterogeneity and therapy resistance. Through cell plasticity, some lung adenocarcinoma (LUAD) cells transform into neuroendocrine (NE) tumor cells. However, the mechanisms of NE cell plasticity remain unclear. CRACD (capping protein inhibiting regulator of actin dynamics), a capping protein inhibitor, is frequently inactivated in cancers. CRACD knockout (KO) is sufficient to de-repress 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 cell plasticity is associated with cell de-differentiation and stemness-related pathway activation. The single-cell transcriptomic analysis of LUAD patient tumors recapitulates that the distinct LUAD NE cell cluster expressing NE genes is co-enriched with impaired actin remodeling. This study reveals the crucial role of CRACD in restricting NE cell plasticity that induces cell de-differentiation of LUAD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Neuroendocrinas / Plasticidad de la Célula / Adenocarcinoma del Pulmón / Neoplasias Pulmonares Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Neuroendocrinas / Plasticidad de la Célula / Adenocarcinoma del Pulmón / Neoplasias Pulmonares Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos