Table 1 Stem cell activation types transforming normal stem cells into cancerous stem cells
Stem cell activation type | Target tissue/organ | Cancer type |
|---|---|---|
Naturally activated stem cell: Inactivation of RB1 gene | Retinoblasts | Retinoblastoma |
Loss of tumor suppressor genes (p53) | Breast | Breast |
Expression of oncogenes (ras, myc) | Brain | Brain |
Hormonal stimulation: estrogen | Breast | Breast |
Inflammation: Crohn disease, inflammatory bowl disease, result in activated cell growth | Colon | Colon |
Viral infection: Hepatitis B and C cause inflammation and extensive cirrhosis | Liver | Liver |
Exposure to irritants like tobacco, asbestos cause inflammation | Lung | Lung |
Bacterial infection: Helicobacter pylori and metal dust exposure cause inflammation | Stomach | Stomach |
Loss of miRNA genes (miR15 and miR16) which act as tumor suppressors | Bone marrow | Chronic lymphoid leukemia |
Enforced expression of miR17-92 cluster which acts as oncogenes | Bone marrow | B cell lymphoma |
DNA methylation at 5-position at cytosine residue within CpGs by Dnmt1 (maintenance methyltranferase), Dnmt3a, 3b (initiate de novo methylation), Dnmt2 | Colon | Colorectal |
Methylation dependent repression of transcription by binding of methyl CpG binding proteins- MECP2, MBD1-4, Kaiso to DNA | Colon | Colorectal |
Histone methylation by H3K4 Mtases, H3K9 Mtases, Suv39h1/Suv39h2, G9a, Eu-H Matse1, ESET/SETDB1 | Prostate | Prostate |
Histone acetylation via histone acetyltransferases (HAT) include Gcn5 family proteins, MYST protein, p300/CBP, TAF250, ACTR/SRC1 nuclear receptor cofactors mediate transcriptional activation | Breast | Breast |
Histone deacetylation silences gene expression via HDAC I family, HDAC II family, Sirtuin family (Sir2) | Bone marrow | Acute myeloid leukemia |
Blockage of DNA accessibility to transcription factors by polycomb group proteins which include Polycomb repressive complexes – PRC1 contains Cbx, Mph, Ring, Bmi-1, Mel18 and PRC2 contains Ezh2, Suz12 and Eed | Bone marrow | B and T cell lymphoma |
Alteration in chromatin accessibility to proteins and restriction endonucleases by the disruption of association of histones with DNA using the energy by ATP hydrolysis via ATP dependent remodeling complexes (SWI2/SNF2 protein, ISWI enzymes, Mi-2/NuRD proteins | Bone marrow | Acute myeloid leukemia |