Table 1 Transcription factors grouped by the biological process of action

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]