Insulin-like growth factor signaling plays a major role in regulating the proliferation and metabolism of normal and malignant cells. IGF-binding proteins play an integral role in modifying IGF actions in a wide variety of cell types. The six IGFBP family members share a high affinity for IGF binding and are structurally related, but are encoded by distinct genes. IGFBPs can exert stimulatory or inhibitory effects by controlling IGF availability through high affinity binding of IGF at the carboxy-terminal domain. IGFBP5 belongs to the high affinity IGF binding family. The effects of IGFBP5 on cancer development are either positive or negative depending on the cancer type. IGFBP5 has been shown to regulate tumor cell survival, apoptosis, migration, and metastasis by mechanism of IGF-dependent or IGF-independent actions. Downregulation of IGFBP5 is associated with therapeutic resistance in breast cancer and esophageal carcinoma. Meanwhile, upregulation of the protein can reverse drug resistance.
[1] Hwa, V. et al. (1999) Endocr Rev 20, 761-87.
[2] Yu, H. and Rohan, T. (2000) J Natl Cancer Inst 92, 1472-89.
[3] Martin, J.L. and Baxter, R.C. (2011) Growth Factors 29, 235-44.
[4] Güllü, G. et al. (2012) Chin J Cancer 31, 266-80.
[5] Hwang, J.R. et al. (2016) Sci Rep 6, 39334.
[6] Ding, M. et al. (2016) Nat Cell Biol 18, 319-27.
[7] Chan, D. et al. (2018) Cells 7, pii: E143. doi: 10.3390/cells7100143.
[8] Wang, W. et al. (2018) Mol Cancer Ther 17, 1973-83.
[9] Leyh, B. et al. (2015) Oncotarget 6, 39307-28.
