Table 1 SRC kinase-mediated signaling transductions in BC

Membrane

HER family proteins

Y845 and Y1101 of EGFR

BC cells

SRC-mediated phosphorylation of EGFR is required for its receptor function, as well as its oncogenic roles in tumor progression

[45]

HER family proteins 

Not reported

BC cells

SRC-mediated phosphorylation is required for ErbB2-mediated oncogenic signaling by positively regulating ErbB2/ErbB3 heterocomplex formation

[46]

TGFβR II

Y284

BC cells

SRC-mediated tyrosine phosphorylation of TGFβRII facilitates the stimulation of TGFβ-p38 MAPK signaling, thereby promoting BC cell proliferation and invasion

[47, 48]

E-cadherin

Y753, Y754 and Y755

Normal epithelial cells

SRC-mediated phosphorylation of E-cadherin disrupts the E-cadherin junctional integrity, and enhances the cell invasive and metastatic abilities

[50,51,52]

E-cadherin 

Y753, Y754 and Y755

TNBC

SRC-mediated phosphorylation of E-cadherin increases its internalization, subsequently destabilizing cell–cell junctions

[53, 54]

Trask

Not reported

BC cells

SRC-mediated Trask phosphorylation is highly relevant to the mitotic regulation of cell adhesion and the epithelial tumorigenesis

[55,56,57]

CDCP1

Y734, 743, 762, 707 and Y806

TNBC

SRC-mediated CDCP1 phosphorylation is linked to the metastatic potential of tumor cells

[56, 58, 59]

Cytoplasm

FAK

Y407, 576 577, 861 and Y925

BC cells and tumor models

SRC-mediated FAK phosphorylation is essential for full FAK activation, and FAK-mediated oncogenic transformation and invasion, and mammary tumor progression in vivo

[62,63,64,65]

Paxillin

Y118 and Y31

BC cells and tumor models

SRC-mediated Paxillin phosphorylation regulates adhesion turnover, which is required for tumor cell invasion and metastasis

[69, 70]

Tensin-3

Y1173, 1206 and Y1256

BC cells

SRC-mediated Tensin-3 phosphorylation contributes to the tumorigenesis and metastasis of BC cells and tumor

[71]

TKS5

Y557 and Y619

BC cells

SRC-mediated TKS5 phosphorylation is required for the podosome formation and SRC-induced invasive phenotypes

[72]

CAV-1

Y14

TNBC

SRC-mediated phosphorylation of CAV-1 is essential for its degradation and promoting BC cell stemness

[73, 74]

LPP

Y245, 301 and Y302

HER2⁺

SRC-mediated LPP phosphorylation is critical for invadopodia formation, BC cell invasion and metastasis

[75]

p190RhoGAP

Y1105

BC cells and tumor models

SRC-mediated p190RhoGAP phosphorylation regulates adhesion turnover, which is required for tumor cell invasion and metastasis

[77,78,79]

PTEN

Y336

BC cells

SRC-mediated PTEN phosphorylation inhibits PTEN function and promotes the PI3K-AKT signaling cascade

[80]

VPS34

Y231

BC cells

SRC-mediated VPS34 phosphorylation is required for the lipid kinase activity of VPS34 and SRC-induced cellular transformation

[81]

AKT

Y315 and Y326

BC cells and tumor models

SRC-mediated AKT phosphorylation is essential for multiple evens of BC development and progressions

[33, 82, 83]

SGK1

Not reported

TNBC

SRC-mediated SGK1 phosphorylation is required for SRC-mediated cell transformation in MCF10A cell

[84]

LATS1

Y692 and Y916

BC cells

SRC-mediated LATS1 phosphorylation abolishes the tumor suppressor activity of LATS1 and induces tumorigenesis in a YAP-dependent manner in BC cells

[85, 86]

CDH1

Y148

TNBC

SRC-mediated CDH1 phosphorylation could disrupt the interaction between Cdh1 and the APC core complex, and thus promote mammary tumorigenesis

[87, 88]

ADAM15B

Y735

BC cells

SRC-mediated ADAM15 phosphorylation is required for ADAM15 protease activity and the subsequent FGFR2 shedding

[89, 90]

LDHA

Y10

BC cells

SRC-mediated LDHA phosphorylation is required for cancer cell invasion, anoikis resistance and tumor metastasis

[91]

Lipin-1

Y398, 413 and Y795

TNBC

Lipin-1 phosphorylation is required for SRC-enhanced glycerolipid synthesis, cell proliferation and xenograft growth in BC

[92, 93]

Nuclear

STATs

Y705 of STAT3 and Y699 of STAT5

EGFR/SRC overexpression

SRC kinase-mediated STAT3/5 activation is required for EGFR/SRC overexpression-induced BC tumorigenesis

[95, 96]

STAT3 

Y705 of STAT3

TNBC

SRC-mediated STAT3 signaling is required for the expression of pluripotency factors and BCSC enrichment in response to chemotherapy

[97]

STAT3 

Y705 of STAT3

NCAPG overexpression-associated HER2⁺

SRC kinase-mediated STAT3 activation is required for NCAPG-induced trastuzumab resistance in HER2⁺ BC

[98]

YAP1 and β-catenin

Y357 of YAP1

RASSF1A-silenced BC

SRC kinase-mediated tyrosine phosphorylation of YAP1 and β-catenin is required for regulating the expression of β-catenin/TBX-YAP/TEAD target genes and the invasive phenotypes of TNBC

[52]

YAP1

Y357

BC-associated fibroblasts

SRC kinase-mediated YAP function is required for BC-associated fibroblasts to promote matrix stiffening, cancer cell invasion and angiogenesis

[99]

YAP1 

Y357

TNBC

SRC kinase-mediated YAP tyrosine phosphorylation is required for glucocorticoids-induced stem cells traits in BC cells

[100]

β-catenin

Y333

TNBC

SRC kinase-mediated β-catenin tyrosine phosphorylation is essential for EGF-induced aggressiveness and metastasis of TNBC cells

[101]

NF-κB p65

Not reported

TNBC

SRC kinase-mediated NF-κB activation is required for CTGF-induced increase in Glut3 expression, glycolytic phenotype and aggressive phenotype of TNBC

[102]

ETS1

Y283

TNBC

SRC-mediated ETS1 phosphorylation could stabilize ETS1 and promote anchorage-independent growth in vitro and tumor growth in vivo

[103]

ER

Y537

Luminal

SRC-mediated ER phosphorylation is necessary for ER binding to the estrogen response element and the monomer to dimer transition

[104, 105]

AR

Y534

TNBC

SRC-mediated AR phosphorylation is required for Kindlin-2-induced BC cell proliferation and migration in vitro and in vivo

[106]

p27

Y74 and Y88

Tamoxifen-resistant BC

SRC kinase-mediated p27 phosphorylation impairs the Cdk2 inhibitory action of p27 and promotes the tamoxifen-resistance in BC

[107, 108]

Sam68

Not reported

BC tumor model

SRC-mediated Sam68 phosphorylation is necessary for mammary tumorigenesis and metastasis

[109]