Abstract
The mechanism underlying the poor prognosis of gastric cancer, including its high degree of malignancy, invasion, and metastasis, is extremely complicated. Rho GTPases are involved in the occurrence and development of a variety of malignant tumors. ARHGAP11A, in the Rho GTPase activating protein family, is highly expressed in gastric cancer, but its function and mechanism have not yet been explored. In this study, the effect of ARHGAP11A on the occurrence and development of gastric cancer and the mechanism related to this effect were studied. The expression of ARHGAP11A was increased in gastric cancer cells and tissues, and high ARHGAP11A expression in tissues was related to the degree of tumor differentiation and poor prognosis. Moreover, ARHGAP11A knockout significantly inhibited cell proliferation, cell migration, and invasion in vitro and significantly inhibited the tumorigenic ability of gastric cancer cells in nude mice in vivo. Further studies revealed that ARHGAP11A promotes the malignant progression of gastric cancer cells by interacting with TPM1 to affect cell migration and invasion and the stability of actin filaments. These results suggest that ARHGAP11A plays an important role in gastric cancer and may become a useful prognostic biomarker and therapeutic target for gastric cancer patients.
Highlights
Cell migration is a complex and dynamic process involving the continuous remodeling of cellular structure [1]
E expression of ARHGAP11A in various types of cancer tissues was further analyzed in the GEPIA2 database, and the mRNA levels of ARHGAP11A in 408 human gastric cancer samples and 211 normal gastric tissues were detected. e results showed that ARHGAP11A was highly expressed in lung cancer, breast cancer, pancreatic cancer, esophageal cancer, gastric cancer, and other types of cancers (Supplementary Figure S1) and that the mRNA expression level of ARHGAP11A was higher in gastric cancer tissues than in adjacent normal tissues (Figure 1(c))
To further explore whether the expression level of ARHGAP11A is correlated with the prognosis of gastric cancer patients, Kaplan-Meier survival analysis was performed on the 432 patients. e prognosis of the ARHGAP11A high-expression group (n 293) was worse than that of the ARHGAP11A low-expression group (n 146) (p 0.0006, Figure 1(i)). is result shows that high expression of ARHGAP11A is related to the poor prognosis of gastric cancer patients
Summary
Cell migration is a complex and dynamic process involving the continuous remodeling of cellular structure [1]. Migration is an important feature of gastric cancer cell spreading during metastasis. Cancer cells must cross the barriers constituted by blood vessels, tissues, and the extracellular matrix. Cancer cells can migrate collectively or individually, and cells can change their migration behavior dynamically and reversibly [2]. Studies have found that Rho GTPases play an important role in the occurrence of malignant tumors, regulating a variety of biological processes, such as cytoskeletal reorganization, cell motility, and cell cycle progression [3]. Rho GTPases cycle between the active GTP-bound state and the inactive GDP-bound state. Is process is regulated by guanine nucleotide exchange factors (GEFs) and Rho GTPase-activating protein (RhoGAP) [4] Rho GTPases cycle between the active GTP-bound state and the inactive GDP-bound state. is process is regulated by guanine nucleotide exchange factors (GEFs) and Rho GTPase-activating protein (RhoGAP) [4]
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