Table 2 Candidate TF regulators selected at 5% FDR for IDC. Functional annotations were determined from terms overrepresented from the canonical pathway gene sets associated with the candidate regulator

ARNT

HIF-1-alpha transcription factor network

 < 2.1E-04

 < 9.1E-10

Downregulation promotes cancer cell migration and invasion

[57]

IL2 signaling events mediated by PI3K

EPHA2 forward signaling

ATF4

PI3K Pathway

 < 1.1E-01

 < 5.9E-10

Critical regulator of the unfolded protein response (UPR) pathway and is implicated in tumorigenesis

[58, 59]

Osteopontin-mediated events

Validated transcriptional targets of deltaNp63 isoforms

FOXA1

FOXA1 transcription factor network

 < 4.7E-10

 < 5.9E-03

Inhibits cell growth via E-cadherin and suppression of ER pathway activation

[40]

FOXA2 and FOXA3 transcription factor networks

Regulation of CDC42 activity

FOXA3_

FOXC2

FOXA2 and FOXA3 transcription factor networks

 < 1.0E-16

 < 9.8E-04

Induces EMT and cancer cell stemness

[60]

Signaling events mediated by HDAC Class II

Regulation of CDC42 activity

FOXD3_

FOXI1_

FOXF1

FOXA1 transcription factor network

 < 2.2E-16

 < 5.7E-06

Downregulation associated with lymph node metastasis in IDC. Potential tumor suppressor affecting the cell cycle. Overexpression associated with EMT

[61,62,63,64]

JNK MAPK Pathway

Hedgehog signaling events mediated by Gli proteins

FOXJ3

FOXA1 transcription factor network

 < 1.0E-16

 < 6.4E-05

Protected motif in chromatin landscape in drug-resistant cancer cells

[65]

Regulation of CDC42 activity

BMP receptor signaling

FOXK1_

FOXP3

FOXA1 transcription factor network

 < 1.0E-16

 < 1.8E-05

Promotes cell proliferation, migration, EMT, and invasion

[66]

Genes encoding enzymes and their regulators involved in the remodeling of the extracellular matrix

Genes encoding proteins affiliated structurally or functionally to extracellular matrix proteins

FOXL1

BMP receptor signaling

 < 1.0E-16

 < 2.1E-11

Functions as a tumor suppressor to inhibit cell proliferation and invasion

[67]

FOXA1 transcription factor network

ErbB4 signaling events

HSF4

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

 < 1.0E-07

 < 1.0E-16

Promotes HIF-1α expression and tumor progression

[68]

Genes encoding structural ECM glycoproteins

Plasma membrane estrogen receptor signaling

PBX3

FOXA1 transcription factor network

 < 1.7E-06

 < 1.0E-16

Attenuates response to Letrozole by potentiating breast cancer cell survival and anchorage-independent growth

[69]

Signaling events mediated by hepatocyte growth factor receptor

(c-Met)

Regulation of androgen receptor activity

PITX1

Coregulation of androgen receptor activity

 < 1.0E-16

 < 1.0E-16

Tumor suppressor that is regulated by ERα

[70]

LKB1 signaling events

Validated targets of C-MYC transcriptional activation

PITX2

ErbB4 signaling events

 < 2.9E-04

 < 1.0E-16

Hypermethylation of PITX2 promoter reduced expression and induced cancer cell progression

[70]

Arf6 trafficking events

RXR and RAR heterodimerization with other nuclear receptors

SPDEF

ErbB2/ErbB3 signaling events

 < 1.3E-01

 < 1.6E-13

Expression is enriched in luminal tumors and promotes differentiation and survival of ER + cells

[71]

Nectin adhesion pathway

Hedgehog signaling events mediated by Gli proteins

ZNF35

Notch signaling pathway

 < 1.4E-02

 < 5.3E-12

Overexpression indicates poor prognosis and lymph node metastasis

[72]

E-cadherin signaling in the nascent adherens junction

IL2 signaling events mediated by PI3K