Vitamin D and the insulin‐like growth factor system: Implications for colorectal neoplasia

Abstract

Epidemiological studies have strongly associated lower levels of vitamin D and its metabolites with an increased risk of colorectal cancer (CRC). The action of calcitriol, the active metabolite of vitamin D, is mediated by the vitamin D receptor (VDR) that is present in most tissues. In advanced CRC, VDR expression is lowered. Calcitriol has several antineoplastic effects in CRC: it promotes the G1‐phase cycle arrest, lowers vascular endothelial growth factor (VEGF) synthesis and acts on tumour stromal fibroblasts to limit cell migration and angiogenesis. Hyperinsulinemia and insulin‐like growth factors (IGFs) have been implicated in the pathophysiology of CRC. IGF‐1 and IGFBP‐3 have been the most studied components of the IGF system. Only 1% of the total serum IGF‐1 is free and bioactive, and 80% of it binds to IGFBP‐3. IGF‐1 and its receptor IGF‐1R are known to induce cell proliferation. Both IGF‐1 and IGFBP‐3 can favour angiogenesis by increasing the transcription of the VEGF gene. A high serum IGF‐1/IGFBP‐3 ratio is associated with increased risk for CRC. VDR is a transcription factor for the IGFBP‐3 gene, and IGF‐1 can increase calcitriol synthesis. Studies examining the effect of vitamin D treatment on serum IGF‐1 and IGFBP‐3 have not been in agreement since different populations, dosages and intervention periods have been used. New vitamin D treatment studies that examine CRC should take in account confounding factors such as obesity or VDR genotypes.

Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

“…In addition, IGF-1 and IGFBP-3 favor angiogenesis by increasing the VEGF gene transcription. An elevated serum ratio for IGF-1/insulin-like growth factor binding protein-3 (IGFBP-3) was associated with increased risk of CRC [ 103 ]. Both IGF-1 and STAT3 can induce CRC development and progression via cell-autonomous and microenvironmental effects [ 82 ].…”

Circular RNA: A promising new star for the diagnosis and treatment of colorectal cancer

“…Among them, the insulin-like growth factor (IGF) plays an important regulatory role in CRC and other malignant tumors, indicating that circRUNX1 can be used as a tumor promoter and is expected to become a potential drug treatment target for CRC. [105][106][107][108][109] In CRC, circPVT1 is upregulated and participates in the proliferation and metastasis of CRC. However, it is noteworthy that overexpression of miR-145 significantly reverses the effect of upregulated circPVT1 on the metastasis of CRC, suggesting that miR-145 is a key downstream effector of circPVT1-mediated CRC metastasis.…”

Maternal VD3supplementation during gestation improves intestinal health and microbial composition of weaning piglets

“…12 Besides, another study also indicated that VD 3 increased the expression of IGF-1R . 43 It has been reported that VDR can increase the expression of serum IGF-1. 44 Thus, the IGF-1/IGF-1R pathway might be one of the mediators for VD 3 /VDR signaling, improving intestinal development and function.…”