Gas6

What is GAS6 Protein?

GAS6 gene (growth arrest specific 6) is a protein coding gene which situated on the long arm of chromosome 13 at locus 13q34. This gene encodes a gamma-carboxyglutamic acid (Gla)-containing protein thought to be involved in the stimulation of cell proliferation. This gene is frequently overexpressed in many cancers and has been implicated as an adverse prognostic marker. Elevated protein levels are additionally associated with a variety of disease states, including venous thromboembolic disease, systemic lupus erythematosus, chronic renal failure, and preeclampsia. The GAS6 protein is consisted of 678 amino acids and GAS6 molecular weight is approximately 74.9 kDa.

What is the Function of GAS6 Protein?

GAS6 protein is a vitamin K-dependent cytokine that binds to members of the TAM family of receptor tyrosine kinases, including Tyro3, Axl, and Mer, and is involved in regulating cell growth, survival, adhesion, and migration. GAS6/Axl signaling plays a role in a variety of biological processes, such as the survival of endothelial cells under acidification conditions, cytokine signaling during natural killer cell development, liver regeneration, survival and migration of gonadotropin-releasing hormone neurons, platelet activation, and regulation of thrombotic response. GAS6 protein expression has been shown to decrease in some cancers, and GAS6 protein may also play an important role in the tumor microenvironment.

Fig1. Role of gas6 in atherosclerosis pathogenesis. (Sandrine Laurance, 2012)

GAS6 Related Signaling Pathway

GAS6 protein, as a key regulator of various biological processes, is involved in several signaling pathways, including Ras-ERK/MAPK, PI3K-Akt, JAK-STAT, etc. It activates these pathways by binding to members of the TAM family of receptor tyrosine kinases (Axl, Tyro3, and MerTK), thereby promoting cell survival, proliferation, migration, and angiogenesis. The GAS6/Axl signaling axis is particularly important in tumor cell invasiveness, metastasis, treatment resistance, and immune escape, and also plays a regulatory role in non-neoplastic diseases such as inflammation and vascular disease. In addition, GAS6 is involved in cell response to apoptotic signals, playing a role in cell fate determination through its anti-apoptotic properties.

GAS6 Related Diseases

GAS6 protein is associated with a variety of diseases, especially in the pathological processes of angiogenesis, inflammation, apoptosis and tumor development. For example, GAS6 plays a key role in promoting tumor cell survival and invasion, regulating platelet function and thrombosis, and participating in immune cell signaling, and its abnormal expression or dysfunction is associated with the development of breast cancer, ovarian cancer, hepatocellular carcinoma, lung cancer and other cancers. It may also be associated with non-neoplastic diseases such as vascular diseases, systemic lupus erythematosus, chronic kidney disease, and preeclampsia.

Bioapplications of GAS6

GAS6 protein has emerged as a potential target for cancer therapy and inflammatory disease intervention due to its key role in cell survival, migration, angiogenesis, and immune regulation. In the field of cancer therapy, small molecule inhibitors, monoclonal antibodies or RNA interference techniques targeting GAS6 or its receptor Axl are being developed to block GAS6-mediated signaling pathways and inhibit tumor cell proliferation and metastasis. In addition, the expression level of GAS6 is also being studied as a biomarker for certain cancers for early diagnosis and prognosis assessment of the disease. In inflammatory diseases, the regulatory role of GAS6 may help control inflammatory processes and provide new ideas for the development of new anti-inflammatory treatment strategies. As a result, GAS6 has a wide range of applications, including drug development, biomarker discovery, and innovation in disease treatment strategies.