Table 1.

Transcription factors grouped by the biological process of action

Transcription factors	Key observations	Reference
Wound healing and fibrosis
Engrailed-1 (EN1)	A major player in wound repair, contributes to the scarring process	[16, 17]
c-Jun/c-fos	Drive AP-1 activation during wound healing in neonatal and adult skin	[10, 18]
SMAD2/3	Downstream to TGF-β signaling activation in fetal and adult wound healing process	[10, 19]
β-catenin	Downstream to Wingless type (Wnt) signaling during wound tissue remodeling	[10, 20]
RUNX1, TCF4, ZEB2	“Wound fibroblast TF signature” contributing to the wound healing process	[15]
TCF4, SOX9, EGR2, FOXS1	Drive myofibroblast differentiation in chronic wounds	[21]
LEF1	Promotes healthy skin regeneration in young skin	[22]
ZFP423	Drives regeneration of fat cells from myofibroblasts during wound healing	[23]
PRRX	Drives a pro-fibrotic response in idiopathic pulmonary fibrosis	[24]
BNC2	Sustains the myofibroblastic activation in liver fibrosis	[25]
Normal fibroblast conversion into CAFs
GLI1	Specific Gli1 + fibroblasts expansion in tumor stroma during carcinogenesis	[26]
TBX4	Lost during lung CAF activation Promotes fibroblast proliferation and collagen gel contraction capacity	[27]
CSL/p53 complex	Lost during early CAF activation Direct repressor of CAF-effector genes. Repressor of p53	[28]
ATF3	Lost during early CAF activation Converges with CSL complex to inhibit CAF-determining genes	[29]
Androgen receptor	- Lost during early CAF activation. Converges with CSL complex to repress key CAF effector genes	[30]
	- AR loss promotes the tumor-promoting abilities of CAFs	[31]
	- AR loss induces deformation of nuclear shape, and nuclear abnormalities and inhibits CAF features	[32]
SMAD2/3	Sustains TGF-β and SDF-1 autocrine signaling required for NF conversion into CAFs	[33]
HSF1	Sustains TGF-β and SDF-1 autocrine signaling	[34]
RUNX3/MYC	Sustains TGF-β autocrine signaling	[35]
YAP-TEAD	Downstream to mechanotransduction and matrix remodeling sustain CAF generation and maintenance	[36]
HSF1/ Dickkopf-3	Positive regulators of YAP nuclear translocation and activation of target gene	[37]
MRTF-SRF	Crosstalk with YAP-TEAD signaling. Downstream to mechano-transduction, induce CAF contractile and pro-invasive properties	[38]
SNAIL1	Downstream to YAP-mediated mechano-transduction Induces fibronectin and collagen expression and promotes matrix rigidity	[39]
ZNF416	Downstream to mechano-transduction, supports fibroblast contractile activation, proliferation, and ECM synthesis	[40]
HIF-1α	Drives metabolic reprogramming in breast cancer cells leading to CAF activation	[41]
POU1F1	Drives metabolic reprogramming of both CAFs and cancer cells	[42]
c-FOS and c-JUN	Modulate the expression of glycolytic enzymes required for CAF activation	[43]
TFAM	Its downregulation in CAFs induces mitochondrial dysfunction and metabolic reprogramming towards aerobic glycolysis promoting tumor cell growth	[44]
RUNX1	Sustains mesenchymal stem cell differentiation into myofibroblasts in prostate cancer stroma	[45]
ZNF32	When expressed in breast tumor cells, leads to CAF transformation from normal fibroblasts	[46]
CAF activation and pro-tumoral functions
SNAIL1	- Sustains CAF activation and pro-tumoral functions across various cancers	[47]
	- Regulates fibroblast activation protein alpha (Fap) expression and promotes immune suppression in melanoma	[48]
TWIST	Sustains Twist1-Prrx1-TNC positive feedback loop	[49]
PRRX1	When depleted, forces CAFs into a highly activated state with increased ECM deposition	[50]
ZEB1	Sustains pro-tumoral CAF features	[51]
RUNX2	Sustains pro-tumoral CAF functions in bladder cancer	[52]
RUNX1	Sustains early activation of CAF-tumor cell crosstalk	[53]
p53	Activates late stage of CAF-specific genes	[54]
ATF3	Activates late stage of CAF-specific genes	[55]
STAT-3	Paracrine pro-tumorigenic CAF functions in breast cancer	[56]
CAF plasticity and heterogeneity
RUNX2	Regulates “early wound CAF” subtype signature	[57]
FOX TFs	Increased activity in precancerous adenomas “intermediate state” during transformation from healthy to colorectal cancer	[58]
RUNX1	Increased activity in cancerous state of colorectal cancer	[58]
MYC	Sustains metastasis-associated fibroblast rewiring in lung cancer	[59]
ZEB1	- Promotes myofibroblastic features of colorectal cancer-derived CAFs	[51]
	- Sustains CAF reprogramming via a secretory program	[60]
PRRX	- Acts as master TFs of stromal fibroblasts for myofibroblastic lineage progression in multiple cancer types	[61]
	- Induces CAF activation in PDAC, allowing a dynamic switch between a dormant and an activated state	[50]
SALL4	Sustains TGF-β-activated CAF subsets in PDAC	[62]
SMAD2	Defines TGF-β-activated myofibroblasts	[33]
SOX2	Drives colonic fibroblasts reprogramming and promotes pro-tumoral myofibroblast functions and immunosuppressive tumor microenvironment	[63]
CAF plasticity and heterogeneity mediated by cancer cell contextual cues
ETV1	- Sustains inflammatory iCAF features. Controls the duality of FGF/TGF-β signaling in skin squamous cell carcinomas	[64]
	- Controls TGF-β /HGF and FGF7 signalling in non-small cell lung cancer	[65]
STAT3	Sustains inflammatory iCAF features induced by tumor-derived IL-1 in naïve pancreatic stellate PDAC cells	[66, 67]
SMAD2	Sustains myCAF features induced by tumor-derived TGF-β in naïve pancreatic stellate PDAC cells	[66, 67]
MZF1	Sustains the mesenchymal stem cells to-myCAF conversion in breast cancer	[68]
RUNX1	Associated with specific TFs network involved in pro-tumoral cancer cell/CAF crosstalk in prostate cancer	[53]
ZEB1	Its expression in tumor cells reprograms CAFs to promote metastasis in lung adenocarcinoma	[46, 60]
ZNF32	Its expression in tumor cells prevents fibroblast activation in breast cancer cells	[46]
P53	Its mutational status in pancreatic cancer cells drives CAF hierarchy to establish a pro-metastatic and chemoresistant TME	[69]