Malignant tumors remain a major global health challenge. The World Health Organization (WHO) reports 19.96 million new cases and 9.74 million deaths annually, reflecting cancer's position as the second leading cause of mortality with a burden that continues to rise [1]. Within the complex molecular networks driving tumorigenic, FOS like-1 (FOSL1, also known as Fra1), a key component of the AP-1 transcription factor complex, acts as a critical regulatory hub. It governs fundamental cellular processes, including cell cycle progression, epithelial-mesenchymal transition (EMT), and remodeling of the tumor microenvironment (TME) [2,3]. Pan-cancer analyses further confirm FOSL1 overexpression across multiple solid tumors (e.g., thyroid, gastric, and breast cancers) and its significant correlation with increased invasiveness and metastasis potential [4], underscoring its promise as a broad-spectrum therapeutic target.

Recent research focusing on neural regulation in the TME has identified perineural invasion (PNI) as an independent of poor prognostic. Concurrently, neurotrophin-mediated crosstalk between tumors and nerves has been shown to promote metastatic spread [5]. Notably, FOSL1 emerges as a central mediator of tumor-neural interactions, with well-documented pivotal roles in driving malignant progression through diverse mechanisms. These mechanisms collectively highlight tumors' dependency on neural signaling, yet FOSL1's multidimensional regulatory roles in tumor-nerve crosstalk, along with its translational therapeutic potential, remain to be systematically delineated.

This review dissects the core oncogenic functions of FOSL1, with specific emphasis on its key mechanisms in mediating tumor-neural interactions (including neural remodeling, signal transduction, and immune coordination) and its clinical translational value (encompassing applications in diagnosis, prognosis, and targeted therapy). Ultimately, this work aims to establish a theoretical framework that underscores FOSL1's significance in advancing both research and clinical applications in the field of cancer neurobiology.