Pathophysiological mechanisms of death resistance in colorectal carcinoma

Table 2 Signaling pathways for modulation of apoptotic regulators in cancer

Pathway	Observation in experimental models	Ref.
PI3K/Akt	Increase of Bcl-2, Bcl-XL and survivin expression in colon cancer cell lines (SW480, SW620, HCT116, and HT29)	[74,75]
	Inactivation of BAD by phosphorylation in colon cancer cell lines (HT29 and H508)	[76,77]
	Decreased expression of Bim and inactivation of Bax in colon cancer cell lines (HCT116 and DLD1), and increase of tumor growth in xenograft models	[78]
MEK/ERK	Phosphorylation and stabilization of Bcl-2 in colon cancer cell lines (HCT116 and HT29) for increase of anoikis, and promotion of metastasis in xenograft models	[80]
	Decreased expression of Bim and inactivation of Bax in colon cancer cell lines (HCT116 and DLD1), and increase of tumor growth in xenograft models	[78]
	Suppression of PUMA expression and activity in colon cancer cell lines (Lovo and SW1116)	[73]
	Dowregulation of XAF1 and upregulation of XIAP in colon cancer cell lines (HCT116, Lovo, DLD1, and SW1116)	[82]
IKK/IκB/NFκB	Induction of cIAP-2 expression in colon cancer cell lines (Caco-2, HCT116, KM20, and KM12C)	[91]
	Increase of Bcl-2, Bcl-XL, and cFLIP in colon cancer cell lines (COLO205 and HCT116)	[92]
HIF	Binding to hypoxia-responsive element of the Bid promoter in colon cancer cells (SW480) for Bid downregulation	[94]
	Binding to hypoxia-responsive element of the survivin promoter in breast cancer cells (MCF-7) for survivin upregulation	[93]

PI3K: Phosphatidylinositide 3-kinase; MEK: Mitogen-activated protein kinase kinase; ERK: Extracellular signal-regulated kinase; NFκB: Nuclear factor kappa B; IκB: Inhibitor of NFκB; IKK: IκB kinase; HIF: Hypoxia-inducible factor.