IGF2R and Associated Diseases
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Overview of IGF2R
Insulin-like growth factor 2 receptor (IGF2R, also known as the cation-independent mannose-6-phosphate receptor or M6P/IGF2R) is a protein encoded by the IGF2R gene in humans. IGF2R is a multifunctional protein receptor, which can not only bind insulin-like growth factor 2 located at the cell surface but also bind the proteins with mannose-6-phosphate tag in the trans-Golgi network. IGF2R is a type I transmembrane protein consisting of a large extracellular domain and a short cytoplasmic tail. The IFG2R is nearly 300 kDa and functions as a dimer. IGF2R has various functions such as the activation of TGF-β and the degradation of IGF2.
Fig.1 The structure of IGF2R. (Wikipedia)
IGF2R in Disease
IGF2R plays an important role in apoptotic pathways and the innate immune system. Ectopic expression of IGF2R may cause a series of diseases such as Mucolipidosis Ii Alpha/Beta, hepatocellular carcinoma, and non-small cell lung cancer.
- Hepatocellular carcinoma
IGF2R is regarded as a tumor suppressor in hepatocellular carcinoma (HCC). IGF2R is located on chromosome 6q25-27, where a liver tumor suppressor is predicted to be contained. As a tumor inhibitor, restored expression of IGF2R will inhibit the growth of the tumor, whereas reduced expression causes increased tumor growth. Polymorphic IGF2R is found in primary HCC patients and half of the patients show loss of heterozygosity (LOH) for IGF2R. Besides, a significant reduction in the overall survival rate and the disease-free survival rate is observed in the patients with IGF2R LOH. Thus, M6P/IGF2R LOH is associated with poor therapeutic outcomes in primary HCC patients.
- Non-small cell lung cancer
Low IGF2R expression is associated with severe non-small cell lung cancer (NSCLC). Insulin-like growth factor pathway sheds new light on the treatment of cancer like NSCLC. When analyzing the data from NSCLC patients, the low expression of IGF2R is related to a higher tumor stage, a stronger resistance to chemotherapy, and a poorer prognosis. In the NSCLC cell line, the knockdown of IGF2R by siRNA increases the proliferation, migration, and invasion abilities, meanwhile, the reduced apoptosis rate is observed. The silenced expression of IGF2R is also associated with enhanced chemotherapy resistance of NSCLC cell lines. In a word, the low IGF2R expression is related to the poor prognosis of patients with advanced NSCLC.
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References
- Jang, H. S.; et al. Clinical significance of loss of heterozygosity for M6P/IGF2R in patients with primary hepatocellular carcinoma. WJG. 2008, 14: 1394.
- Tian, Z.; et al. IGF2R Expression is Associated with the Chemotherapy Response and Prognosis of Patients with Advanced NSCLC. Cell Physiol Biochem. 2014, 34: 1578–1588.
