IMPACT OF SNX5 EXPRESSION ON BREAST CANCER PROGRESSION VIA EGFR-ERK1/2 REGULATION: IMPLICATIONS FOR REHABILITATION AND PHYSICAL ACTIVITY IN CANCER MANAGEMENT

Abstract

Objective: Sorting Nexin 5 (SNX5) is a peripheral protein that plays a role in cell membrane transport and degradation through its involvement in the Retromer complex. While SNX5 is overexpressed in papillary thyroid carcinoma (PTC) tissues, it is under expressed in multiple tumors, including lung, breast, colon, liver, and ovarian cancers, suggesting its involvement in tumorigenesis. This study aims to investigate the role of SNX5 expression in breast cancer progression through its regulation of the EGFR-ERK1/2 signaling pathway, with a focus on its potential implications for rehabilitation, physical activity, and post-cancer functional recovery. Methods: The correlation between SNX5 expression and breast cancer cell proliferation was examined using both in vitro and in vivo experiments. The effect of SNX5 on the cell cycle and tumor progression was analyzed using a combination of molecular and cellular biology techniques. Immunohistochemical staining was performed to assess SNX5 localization in cytoplasm and nucleus. Additionally, the Breast Cancer Prognosis Network (GOBO) was utilized to predict the association between SNX5 expression and clinical outcomes. Eukaryotic expression vectors carrying SNX5 were introduced into breast cancer cell lines using FuGENE® HD transfection, generating SNX5-overexpressing cancer cell models. Further studies examined the effects of EGFR-ERK1/2 pathway modulation on tumor cell growth and proliferation. Results: SNX5 expression was significantly higher in breast cancer tissues compared to adjacent normal tissues. Knockout of SNX5 in breast cancer cell lines resulted in reduced tumor cell growth, while overexpression of SNX5 significantly enhanced proliferation, confirming its role in tumor progression. Mechanistically, SNX5 promoted breast cancer growth and metastasis by activating the ERK1/2 pathway through the inhibition of EGFR entosis and degradation. Conclusion: This study identifies SNX5 as a key regulator of breast cancer progression via the EGFR-ERK1/2 signaling pathway. Given its role in tumor growth and metastasis, SNX5 may serve as a potential therapeutic target for breast cancer treatment. Additionally, understanding the molecular mechanisms of SNX5 in breast cancer progression may provide insights into rehabilitation strategies, exercise interventions, and functional recovery protocols for breast cancer survivors in sports and physical activity settings. Future research should explore how targeting SNX5-related pathways could improve post-treatment rehabilitation, muscle recovery, and physical function in breast cancer patients engaging in exercise-based recovery programs.