Jin, Yujuan, Zhao, Qiqi, Zhu, Weikang, Feng, Yan, Xiao, Tian, Zhang, Peng, Jiang, Liyan, Hou, Yingyong, Guo, Chenchen, Huang, Hsinyi, Chen, Yabin, Tong, Xinyuan, Cao, Jiayu, Li, Fei, Zhu, Xueliang, Qin, Jun, Gao, Dong, Liu, Xin-Yuan, Zhang, Hua, Chen, Luonan, Thomas, Roman K., Wong, Kwok-Kin, Zhang, Lei, Wang, Yong, Hu, Liang and Ji, Hongbin (2022). Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis. Natl. Sci. Rev., 9 (7). OXFORD: OXFORD UNIV PRESS. ISSN 2053-714X

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Abstract

Small-cell lung cancer (SCLC) is a recalcitrant cancer characterized by high metastasis. However, the exact cell type contributing to metastasis remains elusive. Using a Rb1(L/L)/Trp53(L/L) mouse model, we identify the NCAM(hi)CD44(lo/-) subpopulation as the SCLC metastasizing cell (SMC), which is progressively transitioned from the non-metastasizing NCAM(lo)CD44(hi) cell (non-SMC). Integrative chromatin accessibility and gene expression profiling studies reveal the important role of the SWI/SNF complex, and knockout of its central component, Brg1, significantly inhibits such phenotypic transition and metastasis. Mechanistically, TAZ is silenced by the SWI/SNF complex during SCLC malignant progression, and its knockdown promotes SMC transition and metastasis. Importantly, ectopic TAZ expression reversely drives SMC-to-non-SMC transition and alleviates metastasis. Single-cell RNA-sequencing analyses identify SMC as the dominant subpopulation in human SCLC metastasis, and immunostaining data show a positive correlation between TAZ and patient prognosis. These data uncover high SCLC plasticity and identify TAZ as the key molecular switch in orchestrating SCLC phenotypic transition and metastasis.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Jin, YujuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhao, QiqiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhu, WeikangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feng, YanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xiao, TianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, PengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jiang, LiyanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hou, YingyongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guo, ChenchenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huang, HsinyiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen, YabinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tong, XinyuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cao, JiayuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, FeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhu, XueliangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Qin, JunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gao, DongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, Xin-YuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, HuaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen, LuonanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, Roman K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wong, Kwok-KinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, LeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, YongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hu, LiangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ji, HongbinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-691882
DOI: 10.1093/nsr/nwab232
Journal or Publication Title: Natl. Sci. Rev.
Volume: 9
Number: 7
Date: 2022
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 2053-714X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CELL LUNG-CANCER; TUMOR-PROPAGATING CELLS; ORGAN SIZE CONTROL; CARCINOMA PROGRESSION; HIPPO PATHWAY; MOUSE MODEL; GENE; YAP; HETEROGENEITY; INACTIVATIONMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69188

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