Identification of TAZ As the Essential Molecular Switch in Orchestrating SCLC Phenotypic Transition and Metastasis

Overview

Journal Natl Sci Rev

Date 2022 Aug 15

PMID 35967587

Authors

Yujuan Jin

Qiqi Zhao

Weikang Zhu

Yan Feng

Tian Xiao

Peng Zhang

Liyan Jiang

Yingyong Hou

Chenchen Guo

Hsinyi Huang

Yabin Chen

Xinyuan Tong

Jiayu Cao

Fei Li

Xueliang Zhu

Jun Qin

Dong Gao

Xin-Yuan Liu

Hua Zhang

Luonan Chen

Roman K Thomas

Kwok-Kin Wong

Lei Zhang

Yong Wang

Liang Hu

Hongbin Ji

Affiliations

Soon will be listed here.

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 mouse model, we identify the NCAMCD44 subpopulation as the SCLC metastasizing cell (SMC), which is progressively transitioned from the non-metastasizing NCAMCD44 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, , 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.

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