Cell reprogramming in cancer: Interplay of genetic, epigenetic mechanisms, and the tumor microenvironment in carcinogenesis and metastasis

Table 1 Summary of commonly described genes, epigenetic regulators, tumor microenvironment factors, and epithelial-mesenchymal transition factors involved in cell reprogramming and cancer cell plasticity

	Summary of commonly described genes
Key genes in cell reprogramming and cancer plasticity	Oncogenes: KRAS, MYC, EGFR, MET, PIK3CA, BRAF
	Tumor suppressor genes: TP53, RB1, PTEN, CDKN2A, APC
	Stemness/reprogramming genes: OCT4, SOX2, NANOG, KLF4, LIN28, c-MYC
	Neuroendocrine differentiation genes: ASCL1, NEUROD1, DLL3, CHGA, SYP
	EMT-associated transcription factors: SNAIL (SNAI1), SLUG (SNAI2), TWIST1, ZEB1, ZEB2
Epigenetic regulators	Histone modifiers: EZH2, KDM6B, SETDB1, NSD2 (regulate chromatin accessibility)
	DNA methylation enzymes: DNMT1, DNMT3A, DNMT3B, TET1-3 (control gene silencing or activation)
	Chromatin remodelers: SWI/SNF complex (ARID1A, BRG1/SMARCA4) (alter chromatin structure)
	Non-coding RNAs: MiR-200 family, lncRNAs (HOTAIR, MALAT1) (modulate gene expression)
Tumor microenvironment factors	Cytokines & chemokines: IL-6, IL-8, TGF-β, TNF-α, CXCL12, CCL2 (promote inflammation and plasticity)
	Immune cells: Tumor-associated macrophages, myeloid-derived suppressor cells, T-regulatory cells (contribute to immune evasion)
	Hypoxia-induced factors: HIF-1α, VEGF, ANGPT2 (promote angiogenesis and plasticity)
	Fibroblasts & extracellular matrix: Cancer-associated fibroblasts, matrix stiffness (collagen I, fibronectin, hyaluronan)
EMT factors in cancer cell plasticity	Transcription factors: SNAIL, SLUG, TWIST1, ZEB1, ZEB2 (suppress epithelial markers and enhance mesenchymal transition)
	Epithelial markers (downregulated in EMT): CDH1, cytokeratin (KRTs), CLDNs, OCLN
	Mesenchymal markers (upregulated in EMT): VIM, CDH2, FN1
	Signaling pathways driving EMT: TGF-β, WNT/β-catenin, Notch, Hedgehog, PI3K/AKT, NF-κB

EGFR: Epidermal growth factor receptor; BRAF: B-Raf proto-oncogene; PTEN: Phosphatase and tensin homolog; CDKN2A: Cyclin-dependent kinase inhibitor 2A; APC: Adenomatous polyposis coli; OCT4: Octamer-binding transcription factor 4; SOX2: Sex-determining region Y-box 2; KLF4: Kruppel-like factor 4; DLL3: Delta-like ligand 3; CHGA: Chromogranin A; SYP: Synaptophysin; ZEB1: Zinc finger E-box binding homeobox 1; ZEB2: Zinc finger E-box binding homeobox 2; EZH2: Enhancer of zeste homolog 2; SETDB1: SET domain bifurcated 1; NSD2: Nuclear SET domain 2; DNMT: DNA methyltransferase; TET: Ten-eleven translocation; SWI/SNF: SWItch/sucrose nonfermentable; ARID1A: AT-rich interaction domain 1A; BRG1: Brahma-related gene 1; lncRNA: Long noncoding RNA; HOTAIR: HOX transcript antisense RNA; MALAT1: Metastasis associated lung adenocarcinoma transcript 1; IL: Interleukin; TGF: Transforming growth factor; TNF: Tumor necrosis factor; CXCL12: C-X-C motif ligand 12; CCL2: C-C motif ligand 2; HIF-α: Hypoxia inducible factor alpha; VEGF: Vascular endothelial growth factor; ANGPT2: Angiopoietin 2; CDH1: E-cadherin; CLDNs: Claudins; OCLN: Occludins; VIM: Vimentin; CDH2: N-cadherin; FN1: Fibronectin 1; EMT: Epithelial-mesenchymal transition; PI3K: Phosphatidylinositol-3-kinase; AKT: Protein kinase B; NF-κB: Nuclear factor-kappa B.