Hepatoma-derived growth factor (HDGF)

Hepatoma-derived growth factor (HDGF) is a 26-kDa heparin-binding acidic glycoprotein originally identified as a secreted mitogen from the human hepatoma cell line Huh-7 [1, 2]. It is the founding member of a unique gene family characterized by a highly conserved N-terminal HATH (homologous to the amino terminus of HDGF) domain containing a PWWP motif, which facilitates both DNA and RNA binding [10, 11]. HDGF functions through a dual mechanism: it acts as an extracellular growth factor that binds to cell surface receptors to activate pro-survival pathways like MAPK and PI3K/Akt, and it also translocates to the nucleus to function as a transcription factor and chromatin remodeler [2, 8]. In clinical pathology, HDGF is frequently overexpressed in various malignancies, including hepatocellular carcinoma, non-small cell lung cancer, and prostate cancer, where it serves as a potent driver of tumor cell proliferation, angiogenesis, and epithelial-mesenchymal transition [3, 14, 16]. High levels of HDGF in serum or tumor tissue are strongly correlated with increased invasiveness, metastasis, and poor overall survival, making it a valuable prognostic biomarker [1, 16]. Therapeutic strategies targeting HDGF, such as monoclonal antibodies and small molecule inhibitors, are currently being explored to neutralize its oncogenic signaling and inhibit tumor progression [3, 6].

Other names

High mobility group protein 1-like 2HMG-1L2HMG-1-like proteinHeparin-binding growth factor

Neutralization of extracellular HDGF to prevent receptor-mediated signaling (MAPK and PI3K/Akt pathways) and inhibition of intracellular HDGF to disrupt its nuclear mitogenic and transcriptional activities.