Co-targeting TWIST1 and JUNB suppresses CCL2-induced cell motility and hybrid EMT in ESCC models
- 1Hospital of Stomatology, Sun Yat-sen University, Guangzhou Guangdong, PR China
- 2Guangdong Provincial Key Laboratory of Stomatology, Guangzhou Guangdong, PR China
Abstract
The findings demonstrate that upregulation of CCL2 constitutes a significant risk factor for metastatic progression in esophageal squamous cell carcinoma (ESCC), with CCL2 facilitating metastasis through TWIST1-mediated induction of a hybrid epithelial-mesenchymal transition (EMT) phenotype. Notably, inhibition of TWIST1 alone elicits a compensatory activation of JUNB via the PI3K/AKT signaling pathway, thereby preserving EMT plasticity and metastatic potential. To address this adaptive resistance, we developed a dual-targeting strategy aimed at concurrently suppressing TWIST1 and JUNB, which resulted in a synergistic attenuation of metastatic characteristics. In vivo validation using zebrafish and murine models indicated that this combined inhibition restricts metastatic potential. The study concludes that the interplay between TWIST1 and JUNB underpins adaptive resistance mechanisms in CCL2-high ESCC by sustaining a hybrid EMT state, and that dual targeting of these factors disrupts this process, representing a promising therapeutic approach to suppresses CCL2-driven metastasis in preclinical models.
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BibTeX
@article{ling2026cotargeting,
title = {{Co-targeting TWIST1 and JUNB suppresses CCL2-induced cell motility and hybrid EMT in ESCC models}},
author = {Zihang Ling and Wenxin Mu and Dongyao Wang and Chao Lv and Bin Cheng and Xiaoan Tao},
journal = {Communications Biology},
year = {2026},
month = jul,
doi = {10.1038/s42003-026-10572-7},
url = {https://doi.org/10.1038/s42003-026-10572-7},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Co-targeting TWIST1 and JUNB suppresses CCL2-induced cell motility and hybrid EMT in ESCC models
AU - Zihang Ling
AU - Wenxin Mu
AU - Dongyao Wang
AU - Chao Lv
AU - Bin Cheng
AU - Xiaoan Tao
PY - 2026
DA - 2026/07/08
JO - Communications Biology
DO - 10.1038/s42003-026-10572-7
UR - https://doi.org/10.1038/s42003-026-10572-7
AB - The findings demonstrate that upregulation of CCL2 constitutes a significant risk factor for metastatic progression in esophageal squamous cell carcinoma (ESCC), with CCL2 facilitating metastasis through TWIST1-mediated induction of a hybrid epithelial-mesenchymal transition (EMT) phenotype. Notably, inhibition of TWIST1 alone elicits a compensatory activation of JUNB via the PI3K/AKT signaling pathway, thereby preserving EMT plasticity and metastatic potential. To address this adaptive resistance, we developed a dual-targeting strategy aimed at concurrently suppressing TWIST1 and JUNB, which resulted in a synergistic attenuation of metastatic characteristics. In vivo validation using zebrafish and murine models indicated that this combined inhibition restricts metastatic potential. The study concludes that the interplay between TWIST1 and JUNB underpins adaptive resistance mechanisms in CCL2-high ESCC by sustaining a hybrid EMT state, and that dual targeting of these factors disrupts this process, representing a promising therapeutic approach to suppresses CCL2-driven metastasis in preclinical models.
SN - 2399-3642
ER -