FOSL1: The core regulatory hub of tumor-neural interactions and its clinical translational prospects

As a core AP-1 transcription factor, FOS like-1 (FOSL1) drives cell proliferation, differentiation, transformation, and tumorigenesis by regulating downstream targets via heterodimer formation. Pan-cancer analyses confirm its characteristic overexpression in solid tumors, with expression levels strongly correlating with tumor invasiveness and metastasis. Emerging evidence highlights tumor-nerve crosstalk in the tumor microenvironment (TME) as a key driver of progression, and recent studies identify FOSL1 as a central regulatory hub linking tumors and the nervous system. It modulates tumor-neural interactions through mechanisms that include Schwann cell reprogramming, chemokine network construction, axon orientation regulation, synaptic connection modulation, and immune-neuro-tumor synergy, thereby promoting neural remodeling, invasion, metastasis, and TME reprogramming. Elucidating FOSL1's multidimensional regulation of tumor-nerve crosstalk not only offers new insights into tumor neural dependency but also establishes a theoretical basis for developing FOSL1-based diagnostic markers, prognostic tools, and novel targeted therapies, with substantial clinical translational potential.