Table 1 Candidate TF regulators selected at 5% FDR for ILC. Functional annotations were determined from terms overrepresented from the canonical pathway gene sets associated with the candidate regulator

EGR1

Genes encoding, enzymes and their regulators involved in the remodeling of the ECM

 < 1.0E-16

 < 1.0E-16

Overexpression induces E-cadherin transcription inhibition

[43]

Genes encoding secreted soluble factors

Genes encoding structural ECM glycoproteins

HMGA1

E2F transcription factor network

 < 3.4E-03

 < 1.0E-16

Overexpression promotes metastasis

[44]

Genes encoding structural ECM glycoproteins

Regulation of Ras family activation

NFIA

Genes encoding secreted soluble factors

 < 1.0E-16

 < 1.0E-16

Interacts to affect chromatin remodeling

[45]

Ephrin B reverse signaling

ErbB receptor signaling network

NFIX_

NFIB

Genes encoding structural ECM glycoproteins

 < 1.0E-16

 < 1.0E-16

Upregulated in ER + tumors and acts as an oncogene

[46]

Genes encoding secreted soluble factors

Genes encoding enzymes and their regulators involved in the remodeling of the ECM

RBPJ

Genes encoding enzymes and their regulators involved in the remodeling of the ECM

 < 7.6E-01

 < 3.2E-13

Regulates the NOTCH1 pathway via transcriptional repression resulting in recurrence of tumors

[47]

Genes encoding structural components of basement membranes

GMCSF-mediated signaling events

RUNX3_

BCL11A

E-cadherin signaling in keratinocytes

 < 1.0E-16

 < 1.0E-16

RUNX3 inhibits cell proliferation by targeting ERα. BCL11A highly expressed in TNBC, drives metastasis

[38, 48]

TCR signaling in naïve CD4 + T cells

IL12 signaling mediated by STAT4

SOX2

Alpha6 beta4 integrin–ligand interactions

 < 2.2E-04

 < 1.0E-16

Relates to cancer cell stemness, tumorigenicity, and transcription regulation of the CCND1 gene

[49]

Ephrin B reverse signaling

Genes related to regulation of the actin cytoskeleton

SOX4

Genes encoding structural ECM glycoproteins

 < 8.4E-03

 < 1.0E-16

Regulation of EMT-related genes, increased clonogenicity, angiogenesis, and tumor cell dissemination

[50]

Signaling events mediated by the Hedgehog family

Wnt/beta-catenin Pathway

SOX8

Signaling events mediated by the Hedgehog family

 < 7.9E-07

 < 1.0E-16

Relates to cancer cell stemness in TNBC cells

[51]

Genes encoding collagen proteins

Genes encoding structural ECM glycoproteins

STAT6

E-cadherin signaling in keratinocytes

 < 2.4E-07

 < 1.0E-16

Mediates Interleukin-4 (IL-4) growth inhibition, induction of apoptosis

[52]

Netrin-mediated signaling events

Genes encoding structural components of basement membranes

TEAD3_

TEAD1

Ensemble of genes encoding ECM-associated proteins including ECM-affiliated proteins, ECM regulators and secreted factors

 < 1.0E-16

 < 1.0E-16

Bind with HIPPO pathway co-activators (YAP, TAZ) creating oncogenic transformation and tumorigenesis

[53]

Genes encoding enzymes and their regulators involved in the remodeling of the ECM

AMB2 Integrin signaling

TEAD4

Notch-mediated HES/HEY network

 < 8.2E-07

 < 1.0E-16

Overexpressed in BC stem cells and correlate with poor survival

[53]

PDGFR-beta signaling pathway

Genes encoding structural ECM glycoproteins

TP63

Genes encoding secreted soluble factors

 < 1.0E-16

 < 1.0E-16

Enhances endocrine treatment responses in ER + tumors

[54]

Genes encoding structural ECM glycoproteins

Genes encoding enzymes and their regulators involved in the remodeling of the ECM

UBP1

RhoA signaling pathway

 < 1.0E-16

 < 1.0E-16

Overexpressed in breast invasive cancer

[55]

Genes encoding collagen proteins

Genes encoding structural ECM glycoproteins

ZFHX3

Validated targets of C-MYC transcriptional repression

 < 1.4E-03

 < 1.0E-16

Promotes proliferation and tumorigenesis in ER + cells by increasing stemness of cancer cells

[56]

Genes encoding proteins affiliated structurally or functionally to ECM

E-cadherin signaling in keratinocytes