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Fer-mediated activation of the Ras-MAPK signaling pathway drives the proliferation, migration, and invasion of endometrial carcinoma cells

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Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Background

The role of Feline sarcoma-related protein (Fer) in various cancers has been extensively studied, but its specific involvement and underlying mechanisms in the progression of endometrial carcinoma (EC) are yet to be fully understood.

Methods

The expression levels of Fer were assessed in EC tissues and cell lines using real-time quantitative PCR and western blot analysis. CCK-8 assay, Edu staining, transwell assays, and flow cytometry, were conducted to evaluate the impact of Fer on EC cells. Furthermore, a mice xenograft model and immunohistochemistry (IHC) staining were utilized for in vivo analysis. The levels of Ras, pMek1/2, and pErk1/2 were determined by western blot assay. Ras-MAPK signaling pathway inhibitor was utilized to study the regulatory role of Fer on EC cells.

Results

Our findings revealed that Fer exhibited upregulation in both EC tissues and cell lines, concomitant with the activation of the Ras-MAPK signaling pathway. Silencing of Fer resulted in the suppression of cell proliferation, migration, invasion, and Ras-MAPK signaling pathway, while promoted hypoxia-induced apoptosis in RL95-2 and KLE cells. Fer overexpression stimulated cell proliferation, migration, invasion, and Ras-MAPK signaling pathway in Ishikawa and AN3-CA cells, which were reversed after treatment with either Ras or MAPK inhibitor. Moreover, silencing of Fer suppressed tumor growth and downregulated the expression of Ki-67, Ras, pMek1/2, and pErk1/2, but had no significant effect on Mek1/2 and Erk1/2, while upregulated caspase-3 expression in vivo.

Conclusion

In summary, the upregulation of Fer in EC cells resulted in the enhancement of cell proliferation, migration, and invasion through the activation of the Ras-MAPK signaling pathway.

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Data availability

All data are available from the corresponding author with reasonable request.

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Funding

This research is supported by Hainan Natural Science Foundation Youth Foundation project (821QN392) and National Natural Science Foundation to cultivate 530 Project Youth Projects (2021QNXM20).

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Authors and Affiliations

  1. Department of Gynecology, Surgery Building, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), 19Th Xiuhua Road, Xiuying District, Haikou, 570000, China

    Lifan Shen, Kaiying Cui, Xin Liang, Genhai Zhu & Lan Hong

  2. Department of Central Lab, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China

    Chen Zhang

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  1. Lifan Shen
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  4. Xin Liang
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Contributions

(I) Study design/planning: LS; (II) Data collection/entry: LS, CZ, XL, KC; (III) Data analysis/statistics: LS, CZ; (IV) Data interpretation: LS, CZ, GZ, LH; (V) Preparation of manuscript: LS; (VI) Literature analysis/search: All authors; (VII) Funding acquisition: Hainan Natural Science Foundation Youth Foundation project; (VIII) Final approval of manuscript: All authors.

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Correspondence to Lan Hong.

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All the study participants signed an informed consent for the inclusion in the study. The study was approved by Ethical Committee of Hainan General Hospital (No. 2022-597).

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Shen, L., Zhang, C., Cui, K. et al. Fer-mediated activation of the Ras-MAPK signaling pathway drives the proliferation, migration, and invasion of endometrial carcinoma cells. Mol Cell Biochem (2023). https://doi.org/10.1007/s11010-023-04890-1

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