Table 2.
Transcription factors (TFs) in BC pathogenesis studied in 3D culture.
Transcriptional Regulation of | TFs | Target Gene | Proposed Function in breast Carcinogenesis | Cell Lines Used for 3D Culture | Type of ECM | References |
---|---|---|---|---|---|---|
Mammary tissue architecture | P53 | SREBP-1 and SREBP-2 | Disruption of normal acinar morphology via mutant p53 | MDA-468, MDA-231, and MCF10A | rBM matrix | [79] |
NF-κB | Disorganization genes | Disruption of tissue polarity and organization | HMT-3522 S1 and T4-2 cells | rBM matrix | [83] | |
GATA3 | Induces proliferation via mutant GATA3s | ZR751 | Xenograft | [87] | ||
TAZ | IRS1 | Induces proliferation | MCF10A | rBM matrix | [90] | |
SOX7 | SOX7 depletion causes loss of polarity and increased proliferation | MCF10A | rBM matrix | [93] | ||
TBX3 | Branching morphology | MDA-MB-231 | rBM matrix | [198] | ||
MRTF-A and MRTF-B | integrin α5, integrin α6 | Disruption of normal acinar morphology | MCF10A | rBM matrix | [96] | |
Sp1 | Stiffness-induced tumorigenic phenotype and chromatin organization | MCF7 and MDA-MB-231 | rBM matrix | [100] | ||
EMT and metastasis | TWIST1 | ADAM12 | Induces tumor invasion and metastasis | Hs578T and HMLE cells | Matrigel–collagen mixture | [113] |
TWIST1 | PRKD1 | Promotes invasion, epithelial dissemination, and metastasis | murine and human mammary tumor tissues | Organoid | [116] | |
SNAIL | SNAIL inhibition reduces invasion and metastasis | MCF7 | [120] | |||
SNAIL | Downregulation of Snail induces a reversal of EMT in the bone | MDA-MB-231, mammary tumor cells, osteoblast-like cells | rBM matrix | [139] | ||
STAT3 | LINC00520 | Invasion and metastasis | MCF10A-Src transformed cells | rBM matrix, bioprinting | [121] | |
STAT3 | STAT3 inhibition blocks invasion | primary tumor tissue explant culture | rBM matrix | [122] | ||
∆Np63α | ∆Np63α inhibition induces EMT | MCF10A | 3D collagen gel | [126] | ||
OCT1-SOX2, PAX6-SOX2, OCT4-SOX2 | aggressive cancer phenotype | T47D | [130] | |||
SP1, ZNF281, ZNF740, MZF1 and RREB1 | aggressive cancer phenotype | T47D | [130] | |||
ZEB1 | E- and N-cadherins | Induces EMT | HT1080 | rBM matrix | [135] | |
PROX1 | MMP14 | Inhibits invasion | MDA-MB-231 | 3D fibrin matrix | [127] | |
JunB | EMT-induction | NMuMG and iLEC cells | 3D co-culture fibrin beads | [140] | ||
Apoptosis | NF-κB | Induced by tissue polarity and drives resistance to apoptosis | HMT-3522 sourced S-1 and T4-2 cells | rBM matrix | [56] | |
RUNX2 | Bcl-2 and IL-8 | Disruption of normal acinar morphology, increased cell proliferation | MCF10A and MDA-MB-231 | rBM matrix | [91] | |
IRF6 | Induced by detachment and downregulation causes anoikis resistance | MCF10A, HMEC | rBM matrix | [153] | ||
Therapy resistance and drug response | HIF-1α | MDR-1 | Increased resistance to doxorubicin | MCF7 | [173] | |
NF-κB | β1-integrin | Increased radioresistance | HMT-3522 S1 and T4-2 cells | rBM matrix | [176] | |
MYC | Drives resistance to everolimus | MCF7, ZR75, CAMA-1 | rBM matrix | [180] | ||
E2F1, ELK1, GATA, P53 and STAT4 | Increased activity upon lapatinib treatment | MCF10A/ErbBB2 | rBM matrix | [188] | ||
SREBP2 | HMGCR and HMGCS1 | Sensitizes to fluvastatin-induced apoptosis | MDA-MB-231 and MCF7 | rBM matrix | [187] | |
Stemness | SOX2 and FOXO1 | Accumulation of FOXO1 and enhanced SOX2 transcription supports BC stemness | Human breast cancer tissues | ULA plates | [193] | |
NANOG and OCT4 | Increased expression in mammospheres | MCF7 and SKBR3, and MDA-MB-231 | Agar-coated plates | [199] | ||
SOX2, NANOG, OCT4, and FOXO3 | Increased expression in cell surface-GPNMBhigh cells | BT-474, Hs578T, and MDA-MB-468 | ULA or HEMA-coated plates | [201] |