Sesamolin serves as an MYH14 inhibitor to sensitize endometrial cancer to chemotherapy and endocrine therapy via suppressing MYH9/GSK3β/β-catenin signaling

Sep 21, 2026

Endometrial cancer (EC) remains a leading gynecologic malignancy with limited therapeutic effectiveness, partly driven by chemoresistance and endocrine resistance. The study identifies MYH14 as a prognosis-associated myosin family member linked to poor outcomes, enhanced proliferation, and metastatic behavior. Functional and mechanistic experiments show MYH14 impairs responses to carboplatin, paclitaxel, and progesterone by disrupting MYH9-dependent GSK3β/β-catenin ubiquitination and degradation, activating Wnt/β-catenin signaling and epithelial–mesenchymal transition. Sesamolin directly targets MYH14, breaks the MYH14–MYH9 interaction, represses Wnt/β-catenin signaling, and reduces EC progression in vivo without side effects.

LanguageEnglish

CategoryHealthcare

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Pages22

Reading Time55 min

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Abstract

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Lin et al. Cellular & Molecular Biology Letters (2024) 29:63 [https://doi.org/10.1186/s11658-024-00583-9](https://doi.org/10.1186/s11658-024-00583-9) Cellular & Molecular Biology Letters RESEARCH ARTICLE Open Access Sesamolin serves as an MYH14 inhibitor to sensitize endometrial cancer to chemotherapy and endocrine therapy via suppressing MYH9/GSK3β/β-catenin signaling Yibin Lin1†, Xiao Chen2,3†, Linping Lin4, Benhua Xu5*, Xiaofeng Zhu6,9* and Xian Lin7,8* | †Yibin Lin and Xiao Chen
contributed equally to this work. | | --- | | *Correspondence:
[benhuaxu@163.com](benhuaxu@163.com); zhuxiaofengfjmu@163 . com; dentzxf@163.com; [linxiangabriel@fjmu.edu.cn](linxiangabriel@fjmu.edu.cn) | 5 Department of Radiation Oncology, Fujian Medical University Union Hospital, Xinquan Road 29, Gulou District, Fuzhou 350001, Fujian, China 6 Department of Oral Maxillo-Facial Surgery, The First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, Taijing District, Fuzhou 350005, Fujian, China 7 Shenzhen Key Laboratory of Inflammatory and Immunology Diseases, No. 1120 Lianhua Road, Futian District, Shenzhen 518036, Guangdong, China Full list of author information is available at the end of the article Abstract Background: Endometrial cancer (EC) is one of the most common gynecological cancers. Herein, we aimed to define the role of specific myosin family members in EC because this protein family is involved in the progression of various cancers. Methods: Bioinformatics analyses were performed to reveal EC patients’ prognosisassociated genes in patients with EC. Furthermore, colony formation, immunofluorescence, cell counting kit 8, wound healing, and transwell assays as well as coimmunoprecipitation, cycloheximide chase, luciferase reporter, and cellular thermal shift assays were performed to functionally and mechanistically analyze human EC samples, cell lines, and a mouse model, respectively. Results: Machine learning techniques identified MYH14, a member of the myosin family, as the prognosis-associated gene in patients with EC. Furthermore, bioinformatics analyses based on public databases showed that MYH14 was associated with EC chemoresistance. Moreover, immunohistochemistry validated MYH14 upregulation in EC cases compared with that in normal controls and confirmed that MYH14 was an independent and unfavorable prognostic indicator of EC. MYH14 impaired cell sensitivity to carboplatin, paclitaxel, and progesterone, and increased cell proliferation and metastasis in EC. The mechanistic study showed that MYH14 interacted with MYH9 and impaired GSK3β-mediated β-catenin ubiquitination and degradation, thus facilitating the Wnt/β-catenin signaling pathway and epithelial–mesenchymal transition. Sesamolin, a natural compound extracted from Sesamum indicum (L.), directly targeted MYH14 and attenuated EC progression. Additionally, the compound disrupted the interplay between MYH14 and MYH9 and repressed MYH9-regulated Wnt/β-catenin signaling. The in vivo study further verified sesamolin as a therapeutic drug without side effects. Conclusions: Herein, we identified that EC prognosis-associated MYH14 was independently responsible for poor overall survival time of patients, and it augmented EC progression by activating Wnt/β-catenin signaling. Targeting MYH14 by sesamolin, © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended

FAQs

What role does MYH14 play in endometrial cancer prognosis?

MYH14 is identified as a prognosis-associated gene and an unfavorable independent prognostic indicator in endometrial cancer patients.

How does MYH14 influence chemotherapy and endocrine therapy sensitivity?

MYH14 reduces cellular sensitivity to carboplatin, paclitaxel, and progesterone while promoting proliferation and metastasis.

How does sesamolin affect MYH14-driven signaling in EC?

Sesamolin directly targets MYH14, disrupts MYH14–MYH9 interaction, and represses MYH9-regulated Wnt/β-catenin signaling, thereby attenuating EC progression.

Sep 21, 2026

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