DOCK1 regulates the malignant biological behavior of endometrial cancer through c-Raf/ERK pathway

Background: The role of the DOCK1 gene in regulating the biological behavior of endometrial carcinoma cells and its associated pathways remains unexplored.
Methods: Immunohistochemistry and western blot analyses were employed to assess DOCK1 protein expression in endometrial tissues and cells. The effects of altered DOCK1 expression on the viability, proliferation, invasion, migration, and apoptosis of endometrial cancer cells were examined using CCK-8, BrdU, Transwell assays, and flow cytometry. Western blot was used to evaluate the impact of DOCK1 on Bcl-2, MMP9, Ezrin, E-cadherin, and the c-RAF/ERK1/2 signaling pathway. Additionally, xenograft models were established to study the in vivo effects of DOCK1.
Results: DOCK1 expression was significantly elevated in endometrial cancer tissues and cells compared to adjacent normal tissues and cells. DOCK1 knockout inhibited the malignant behavior of endometrial cancer cells, whereas its overexpression promoted these behaviors. Following DOCK1 knockout, E-cadherin expression increased, while MMP9, Ezrin, Bcl-2, p-c-RAF (S338), and p-ERK1/2 (T202/Y204) levels decreased. Conversely, DOCK1 overexpression had the opposite effects. Treatment with the Raf inhibitor LY3009120 reversed the pro-malignant effects of DOCK1. In vivo, DOCK1 knockout suppressed tumor growth and weight in nude mice, and the expression changes of E-cadherin, MMP9, Ezrin, and Bcl-2 in xenograft tumors mirrored the in vitro findings.
Conclusion: DOCK1 promotes the malignant behavior of endometrial cancer cells, potentially via activation of the c-RAF/ERK1/2 signaling pathway in both in vitro and in vivo models.