Eno2, also known as neuron-specific enolase (NSE), is a crucial glycolytic enzyme [4]. It is a cell-specific isoenzyme of enolase, with its expression being a late event in neural differentiation, making it a useful index of neural maturation [4]. Eno2 is highly specific for neurons and peripheral neuroendocrine cells and is involved in various biological processes, especially those related to cancer metabolism [4].

In cancer research, Eno2 has been found to play significant roles. In colorectal cancer (CRC) mouse models, Eno2 overexpression induces neuroendocrine differentiation, promotes malignant behavior, and confers resistance to anti-angiogenic therapy. The Eno2-derived metabolite phosphoenolpyruvate (PEP) selectively inhibits histone deacetylase 1 (HDAC1) activity, activating the β-catenin pathway [1]. In head and neck squamous cell carcinoma (HNSCC), Eno2 is required for cell proliferation and glycolysis, partially achieved by controlling PKM2 protein stability and its nuclear translocation. Treatment with the ENO inhibitor AP-III-a4 significantly induces HNSCC remission in preclinical mouse models [2]. In diffuse large B-cell lymphoma (DLBCL), DLBCL-derived exosomal ENO2 modulates macrophage polarization via glycolysis and the GSK3β/β-catenin/c-Myc signaling pathway, promoting DLBCL progression [3].

In conclusion, Eno2 is an important glycolytic enzyme with a role in neural maturation. In the context of cancer, Eno2-related research, especially through animal models, has revealed its significance in promoting tumorigenesis, metastasis, and drug resistance in various cancers such as CRC, HNSCC, and DLBCL. Understanding Eno2's functions provides potential therapeutic targets and prognostic biomarkers for these diseases.