Further, loss of OXPHOS genes SLC25A5, ATP6V1B1, B3, V0A4, and NDUFA4 may contribute to the self-sufficiency of the cancer cells with the ability to be less dependent on OXPHOS (2) The loss of tumor suppressor genes PTPRO, TFAP2A, CDKN1C, AIM1 and MT1G as well as other genes that were shown to suppress tumor growth in cancer cell lines but not yet identified as tumor suppressor candidates (RASD1, VDR, EHF, SPP1, ACPP, MT1F and ERBB4) contributes to insensitivity to antigrowth signals; (3) Evasion of apoptosis is mediated through loss of SPP1 and SFRP1, and activation of TUBB, NOL3 and EGLN3. (4) Two groups of genes are likely to be involved in tissue invasion and metastasis: proteolysis genes (PAPPA, PSMB9 and MARCH-1) and genes involved in cell-adhesion and/or regulation of actin cytoskeleton (CNGLN, ITPR2, NPHS1, ITGB2, CLD1, ZAK, WASF2, CD81) and (5) Angiogenesis may be mediated through ALDOA enzyme which is shown to be activated by HIF1 under hypoxic conditions and by increased glycolytic activity (Warburg effect), and which in a feedback loop activates HIF1 (Lu et al. 2002) which then activates several angiogenic factors including VEGF.
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