Impact of Fetuin-A (AHSG) on Tumor Progression and Type 2 Diabetes.
Josiah OchiengGladys NangamiAmos SakweCierra MoyeJoel AlvarezDiva WhalenPortia ThomasPhilip LammersPublished in: International journal of molecular sciences (2018)
Fetuin-A is the protein product of the AHSG gene in humans. It is mainly synthesized by the liver in adult humans and is secreted into the blood where its concentration can vary from a low of ~0.2 mg/mL to a high of ~0.8 mg/mL. Presently, it is considered to be a multifunctional protein that plays important roles in diabetes, kidney disease, and cancer, as well as in inhibition of ectopic calcification. In this review we have focused on work that has been done regarding its potential role(s) in tumor progression and sequelae of diabetes. Recently a number of laboratories have demonstrated that a subset of tumor cells such as pancreatic, prostate and glioblastoma multiform synthesize ectopic fetuin-A, which drives their progression. Fetuin-A that is synthesized, modified, and secreted by tumor cells may be more relevant in understanding the pathophysiological role of this enigmatic protein in tumors, as opposed to the relatively high serum concentrations of the liver derived protein. Lastly, auto-antibodies to fetuin-A frequently appear in the sera of tumor patients that could be useful as biomarkers for early diagnosis. In diabetes, solid experimental evidence shows that fetuin-A binds the β-subunit of the insulin receptor to attenuate insulin signaling, thereby contributing to insulin resistance in type 2 diabetes mellitus (T2DM). Fetuin-A also may, together with free fatty acids, induce apoptotic signals in the beta islets cells of the pancreas, reducing the secretion of insulin and further exacerbating T2DM.
Keyphrases
- type diabetes
- glycemic control
- insulin resistance
- cardiovascular disease
- protein protein
- end stage renal disease
- chronic kidney disease
- amino acid
- fatty acid
- prostate cancer
- ejection fraction
- binding protein
- poor prognosis
- adipose tissue
- weight loss
- dna methylation
- induced apoptosis
- high fat diet
- genome wide
- polycystic ovary syndrome
- long non coding rna
- childhood cancer
- drug delivery
- peritoneal dialysis
- cancer therapy
- protein kinase
- skeletal muscle
- high fat diet induced