MYO3B promotes cancer progression in endometrial cancer by mediating the calcium ion-RhoA/ROCK1 signaling pathway

J Cancer Res Clin Oncol. 2024 Sep 19;150(9):424. doi: 10.1007/s00432-024-05940-x.

Abstract

Purpose: This study aimed to investigate the effect of MYO3B on endometrial cancer (EC) proliferation and invasion.

Methods: The expression of MYO3B in EC tissues and cells was analyzed using TCGA database, immunohistochemical staining, real-time PCR, and western blot (WB). Cell proliferation was detected by CCK8, Annexin V-APC/PI flow cytometry was used to detect apoptosis, intracellular calcium ion (Ca2+) was detected by flow cytometry with Fluo-4 AM fluorescent probe, cell migration by scratch assay, and cell invasion by Transwell assay, and the expression of proteins related to Ca2+ homeostasis and RhoA/ROCK1 signaling pathway was detected by WB and immunofluorescence staining.

Results: The expression of MYO3B was an influential factor in EC recurrence, and the expression of MYO3B was significantly up-regulated in EC tissues and cells, but down-regulated in KLE cells, and MYO3B knockdown inhibited the proliferation, migration, and invasion ability of EC cells and promoted apoptosis, suggesting that MYO3B plays a tumor-promoting role in EC. Furthermore, MYO3B knockdown decreased Ca2+ concentration in EC cells and the RhoA/ROCK1 signaling pathway was inhibited, and the effect of MYO3B knockdown on RhoA/ROCK1 signaling was reversed by treatment with the Calmodulin agonist CALP-2, and the effects of MYO3B knockdown on cell proliferation, migration, and invasion were reversed after treatment with the RhoA agonist U-46,619.

Conclusion: MYO3B promotes the proliferation and migration of endometrial cancer cells via Ca2+-RhoA/ROCK1 signaling pathway. High expression of MYO3B may be a biomarker for EC metastasis.

Keywords: Calcium/calmodulin; Cell proliferation; Endometrial cancer; Myosin 3B; RhoA/ROCK1 signaling.

MeSH terms

  • Apoptosis
  • Calcium* / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Disease Progression*
  • Endometrial Neoplasms* / genetics
  • Endometrial Neoplasms* / metabolism
  • Endometrial Neoplasms* / pathology
  • Female
  • Humans
  • Neoplasm Invasiveness
  • Signal Transduction*
  • rho-Associated Kinases* / genetics
  • rho-Associated Kinases* / metabolism
  • rhoA GTP-Binding Protein* / metabolism

Substances

  • rho-Associated Kinases
  • rhoA GTP-Binding Protein
  • ROCK1 protein, human
  • RHOA protein, human
  • Calcium