HGF Assay Portfolio Service

The Biology of HGF

Hepatocyte growth factor (HGF) is known as a paracrine cellular growth and motility and morphogenic factor. It is secreted by mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial origin after binding to the protooncogenic c-MET receptor. HGF is a heterodimer with a larger α subunit and smaller β subunit with homology to tissue plasminogen. HGF is secreted as a precursor polypeptide (proHGF, 92 kDa) bound to heparin proteoglycans in the extracellular matrix. The inactive HGF polypeptide is cleaved by a serine protease at sites of tissue injury and by tumor cells/matrix into active HGF. Active HGF consists of a heavy chain (62 kDa) and a light chain (32-36 kDa), which are linked by a disulfide bridge. HGF exerts potent mitogenic, motogenic, morphogenic, and anti-apoptotic properties on epithelial and endothelial cells. In addition, HGF promotes apoptosis of myofibroblast and inhibition of epithelial-to-mesenchymal cell transition (EMT). HGF acts as an anti-fibrotic agent that protects the host against transforming growth factor-beta (TGF-β) mediated pro-fibrotic effects.

HGF/c-MET Signaling Pathway

After HGF binding to the c-Met receptor, there is an activation of a signaling cascade that increases several biological actions (proliferation/differentiation, survival, and motogenesis). Upon HGF binding to its receptor MET, the receptor undergoes autophosphorylation in the tyrosine kinase domain, resulting in the recruitment of various intracellular signaling proteins, which includes growth factor receptor-bound protein 2 (GRB2), Src homology-2 containing (SHC), v-crk sarcoma virus CT10 oncogene homolog (CRK), phosphatidylinositol 3-kinase (PI3K) and the transcription factor signal transducer and activator of transcription (STAT-3). HGF-MET signaling through PI3K-AKT leads to cell survival and angiogenesis. HGF-MET signaling through focal adhesion kinase (FAK) results in cellular migration. HGF-MET activation generates signaling pathways involved in proliferation, migration, and invasion via Ras/Raf/MEK/Erk1/2. HGF-MET signaling through PI3K/Akt-p53-mTor leads to the anti-apoptotic effect. MET signaling through CRK-dependent Janus kinase 1 (JNK) leads to transformation. STAT mediated MET signaling also results in the transformation and tubulogenesis.

HGF-MET signaling pathway. Fig.1 HGF-MET signaling pathway. (Parikh, 2014)

What Can We Offer?

Activation of HGF-MET signaling induces proliferation and survival, migration, invasion and metastasis, angiogenesis and stromal cell communication, cancer stem cell traits, therapeutic resistance, and EMT. Creative Biolabs provides a series of HGF assay portfolio services, including:

Creative Biolabs develops and commercializes a full range of tumor marker assay services for our customers. We develop and apply the best assay technology for research to improve biotech and pharma discovery timelines and costs. With advanced technology and a professional academic team, Creative Biolabs makes it easy to advance your project successfully. Please feel free to contact us for more information.

Reference

  1. Parikh, R.A.; et al. The potential roles of hepatocyte growth factor (HGF)-MET pathway inhibitors in cancer treatment. OncoTargets and Therapy. 2014, 7: 969-983.

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