Piezo1 regulates actin cytoskeleton remodeling to drive EMT in cervical cancer through the RhoA/ROCK1/PIP2 signaling pathway.

Abstract

Background: Piezo1 has been identified as an oncogenic factor in various types of cancer. The objective of this study was to explore the mechanisms of Piezo1 in cervical cancer invasion and migration, with a focus on its influence on actin cytoskeleton remodeling.

Methods: Immunohistochemistry, western blot, and dot blot assays were employed to evaluate the expression levels of Piezo1, PIP2, and F-actin in cervical cancer. Lentiviral transduction or Yoda1 treatment was used to silence or activate Piezo1. Phalloidin staining was applied to examine the actin cytoskeleton in HeLa and SiHa cells. Transwell assays were conducted to evaluate the invasive and migratory capabilities of the cells. Dot blot and ELISA assays were performed to measure the PIP2 content on the cell membrane. Western blot or qRT-PCR was used to assess the expression levels of EMT markers, RhoA, and ROCK1.

Results: Piezo1, PIP2, and F-actin were upregulated in cervical cancer tissues, with the highest levels observed in tissues from patients with lymph node metastasis. Silencing Piezo1 downregulated the expression of F-actin and disrupted the organization of actin filaments. This cytoskeletal disruption served as an upstream event that inhibited EMT, as well as the invasion and migration of cervical cancer cells. Mechanistically, Piezo1 activated the RhoA/ROCK1 pathway, which in turn increased PIP2 levels in cervical cancer cells, leading to actin cytoskeleton remodeling in these cells.

Conclusion: Piezo1 drives actin cytoskeleton remodeling through the RhoA/ROCK1/PIP2 signaling pathway, thereby promoting EMT, invasion, and migration in cervical cancer. Targeting Piezo1 may offer a novel therapeutic strategy, potentially improving patient outcomes.