Relation of the IGF/IGF1R system to autophagy in colitis and colorectal cancer

Table 1 Modulation of the IGF1R-autophagy crosstalk may induce controversial therapeutic effects

Inducing effects/therapeutic agents	Corresponding cellular actions/processes		Final outcome
Resveratrol	mTOR inhibition ↑	Autophagy induction ↑	IGF1-induced fibrosis ↓
	IGF1R inhibition ↑
	SIRT1 activation ↓
Targeted inhibition of IGF1	IGF1/IGF1R signaling ↓	Altered autophagy machinery	Amelioration of colitis
Modifying IGF1 stability	IGF1/IGF1R signaling ↓	Altered autophagy machinery	Amelioration of colitis
Chronic inflammation	IGF/IGF1R signaling ↑	Altered autophagy machinery;	Pro-tumor effect ↑
		Survival and proliferation of cells bearing genetic errors ↑
Chronic inflammation + small molecule RTK inhibitors	IGF/IGF1R signaling ↓	Survival and proliferation of cells bearing genetic errors ↓	Pro-tumor effect ↓
Targeted inhibition of IGF1R	IGF1R signaling ↓	Cell-protective autophagy ↑	Efficacy of IGF1R targeting ↓
Targeted inhibition of IGF1R +	IGF1R signaling ↓	Cell-protective autophagy ↓	Efficacy of IGF1R targeting ↑
Autophagy disrupting agents
BCAA	IGF1R activation ↓	Insulin-induced cell proliferation ↓	Anti-tumor effect ↑
IGF1R/EGFR inhibition +	IGF1R activation ↓	Cell-protective autophagy ↓	Anti-tumor effect ↑
Increasing miR216b level + autophagy blocking

mTOR: Mammalian target of rapamycin; IGF/1R: Insulin-like growth factor/receptor-1; SIRT: Sirtuin; RTK: Receptor tyrosine kinase; BCAA: Branched chain amino acid; EGFR: Epidermal growth factor receptor.