RAC1 promotes the occurrence and development of tongue squamous cell carcinoma by regulating RAC1/PAK1/LIMK1 signaling pathway

Abstract

Abstract Tongue squamous cell carcinoma (TSCC) remains an unsolved medical problem due to its poor local recurrence rate and prognosis. The purpose of this study was to investigate the expression characteristics of RAC-related C3 botulinum toxin substrate 1(RAC1) in TSCCS and its role in tumor invasion and metastasis. In this study, immunohistochemical staining was used to detect RAC1 expression in 150 tongue cancer specimens. The correlation between RAC1 and clinical-pathological characteristics is analyzed, along with the association between protein levels and disease-specific survival, metastasis-free survival, and local recurrence-free survival. In vitro experiments, RAC1 was knocked down by short hairpin RNA transfection to reveal the role of RAC1 in the invasion and metastasis of TSCC. The regulatory effects of RAC1 on CAL27 cell migration and invasion were evaluated by scratch and invasion methods. The influence of RAC1 expression on tumor growth was scrutinized using a subcutaneous transplant model in nude mice. RAC1 is overexpressed in TSCC and positively correlates with tumor invasion and metastasis. Moreover, elevated RAC1 expression is associated with poorer differentiation. Survival analysis further indicates that high expression of RAC1 is linked to increased recurrence and metastasis rates, as well as poorer prognosis. Additionally, both in vivo and in vitro studies demonstrate that RAC1 may impact tumor progression by modulating the epithelial–mesenchymal transition process through the RAC1/PAK1/LIMK1 signaling pathways. RAC1 overexpression is closely related to the progression of TSCC, and may provide a new prognostic indicator and therapeutic target for tongue cancer.

Keywords

• RAC1
• Tongue squamous cell carcinoma
• Prognosis
• Metastasis
• EMT