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Copyright ©The Author(s) 2015.
World J Gastroenterol. Nov 7, 2015; 21(41): 11777-11792
Published online Nov 7, 2015. doi: 10.3748/wjg.v21.i41.11777
Table 1 Alteration of apoptotic and necroptotic regulators in human colon cancers
ClassificationMoleculeExpression in cancer tissuesRef.
Bcl-2 familyBcl-XLIncreased[56]
IAP familycFLIPIncreased[57]
cIAP2Increased[59,60]
survivinIncreased[55,61]
XIAPIncreased[58]
RIP kinase familyRIPK1/RIPK3Decreased[62]
Table 2 Signaling pathways for modulation of apoptotic regulators in cancer
PathwayObservation in experimental modelsRef.
PI3K/AktIncrease 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/ERKPhosphorylation 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/NFκBInduction 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]
HIFBinding 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]
Table 3 Glucose-dependent mechanisms in death resistance of colon cancer
ClassificationMoleculeExpression and mechanismRef.
Glucose uptake
TransportersGLUT1Abnormal expression of GLUT1 in colon cancer[128,129]
Hypoxia-induced expression of GLUT1 by HIF-1 binding to the GLUT1 promoter[96,131,132]
GLUT1-mediated glucose uptake promoted drug resistance in colon cancer cells[136]
GLUT3,4Abnormal expression of GLUT3,4 in colon cancer[19,27,130]
SGLT1Abnormal expression of SGLT1 in colon cancer[27,115]
Stabilization of membrane SGLT1 expression is dependent on EGFR in a kinase-independent mechanism[117,134]
Glucose metabolism
EnzymesPKUpregulation of PKM2 isoform in chemoresistant cancer cells[132]
PDK-1PDK-1 as a novel Wnt target gene improved colon cancer cell survival via enhancement of glycolysis[142]
PDK-3HIF1-mediated upregulation of PDK-3 inhibited mitochondrial phosphorylation and promoted drug resistance[143]
HK, GAPDHHIF1-dependent transcriptional upregulation[45,96]
PDHDecreased expression in colon cancer cells[141]
CarriersMPCReduction of MPC activity promoted glycolysis and maintenance of stemness properties[144]
ProductsATPElevation of intracellular ATP promoted cancer cell survival and induced drug resistance[145,146]
PyruvatePyruvate prevented hypoxia-induced necroptosis through suppression of mitochondrial free radicals in an ATP-independent mechanism[19]