Quercetin upregulates TLE4 to block the Wnt/β-catenin signaling pathway and inhibit cell migration and invasion of cervical cancer cells
4 affiliations
- 1The Second Clinical Medical College, Shaanxi University of Chinese Medicine
- 2The Second Affiliated Hospital, Shaanxi University of Chinese Medicine
- 3The First Clinical Medical College, Yanan University
- 4Institute of Integrated Traditional Chinese and Western Medicine for Oncology of the Second Affiliated Hospital, Shaanxi University of Chinese Medicine
Abstract
Methods: Using established TLE4-overexpression and CRISPR-Cas9-knockout cervical cancer cell lines and nude mouse tumorigenesis models, we verified the biological function and regulatory mechanism of TLE4 in cervical cancer.
Results: Quercetin treatment upregulated the expression of TLE4 in HeLa cells. Compared with normal cervical tissues from clinical specimens, the expression of TLE4 in the nucleus of cervical cancer tissues was significantly downregulated. Transwell assays showed that the migration and invasion of C-33A TLE4-overexpression cells were significantly suppressed, accompanied by an upregulation of the expression of E-cadherin and a downregulation of the expression of N-cadherin, Vimentin, and Snail. Conversely, the migration and invasion of Ca Ski TLE4-knockout cells were significantly enhanced, and the expressions of these EMT-related markers showed the opposite trend. Meanwhile, the in vivo xenograft experiment revealed that the Ca Ski TLE4-knockout group exhibited faster tumor growth compared with the wild-type group. Furthermore, we examined the role of TLE4 in the Wnt/β-catenin signaling pathway. In C-33A TLE4-overexpression cells, β-catenin, TCF-1, TCF-4, CyclinD1, c-Myc, and MMP-7 were decreased, p-β-catenin expression was increased, whereas in Ca Ski TLE4-knockout cells, the expression trends of these factors were opposite. After treating TLE4-knockout Ca Ski cells with quercetin, the enhanced migration and invasion capabilities induced by TLE4 knockout were effectively reversed.
Conclusion: Quercetin targets and upregulates the expression of TLE4, which inhibits the migration and invasion of cervical cancer cells by blocking the Wnt/β-catenin signaling pathway, thereby providing theoretical and experimental evidence for quercetin therapy in cervical cancer.
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BibTeX
@article{mai2026quercetin,
title = {{Quercetin upregulates TLE4 to block the Wnt/β-catenin signaling pathway and inhibit cell migration and invasion of cervical cancer cells}},
author = {Yirui Mai and Keyi Ju and Yongkang Yang and Weijing Wang and Ting Zhang and Jiake Wang and Yu Wang and Weihua Gao and Tuanwang Li and Beier Gong and Yuanyuan Li},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1892382},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1892382/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Quercetin upregulates TLE4 to block the Wnt/β-catenin signaling pathway and inhibit cell migration and invasion of cervical cancer cells
AU - Yirui Mai
AU - Keyi Ju
AU - Yongkang Yang
AU - Weijing Wang
AU - Ting Zhang
AU - Jiake Wang
AU - Yu Wang
AU - Weihua Gao
AU - Tuanwang Li
AU - Beier Gong
AU - Yuanyuan Li
PY - 2026
DA - 2026/10/07
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1892382
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1892382/full
AB - Methods: Using established TLE4-overexpression and CRISPR-Cas9-knockout cervical cancer cell lines and nude mouse tumorigenesis models, we verified the biological function and regulatory mechanism of TLE4 in cervical cancer. Results: Quercetin treatment upregulated the expression of TLE4 in HeLa cells. Compared with normal cervical tissues from clinical specimens, the expression of TLE4 in the nucleus of cervical cancer tissues was significantly downregulated. Transwell assays showed that the migration and invasion of C-33A TLE4-overexpression cells were significantly suppressed, accompanied by an upregulation of the expression of E-cadherin and a downregulation of the expression of N-cadherin, Vimentin, and Snail. Conversely, the migration and invasion of Ca Ski TLE4-knockout cells were significantly enhanced, and the expressions of these EMT-related markers showed the opposite trend. Meanwhile, the in vivo xenograft experiment revealed that the Ca Ski TLE4-knockout group exhibited faster tumor growth compared with the wild-type group. Furthermore, we examined the role of TLE4 in the Wnt/β-catenin signaling pathway. In C-33A TLE4-overexpression cells, β-catenin, TCF-1, TCF-4, CyclinD1, c-Myc, and MMP-7 were decreased, p-β-catenin expression was increased, whereas in Ca Ski TLE4-knockout cells, the expression trends of these factors were opposite. After treating TLE4-knockout Ca Ski cells with quercetin, the enhanced migration and invasion capabilities induced by TLE4 knockout were effectively reversed. Conclusion: Quercetin targets and upregulates the expression of TLE4, which inhibits the migration and invasion of cervical cancer cells by blocking the Wnt/β-catenin signaling pathway, thereby providing theoretical and experimental evidence for quercetin therapy in cervical cancer.
SN - 1663-9812
ER -