Table 2 Proteins up-regulated in tissue of sentinel lymph node with metastasis as compared to sentinel lymph node without metastasis.

From: iTRAQ proteomics of sentinel lymph nodes for identification of extracellular matrix proteins to flag metastasis in early breast cancer

S.No

Protein

Accesion no.

Avg. ratio of SLNM + /SLNM-

Functions

Relevance in our study

References

1

Alpha-crystallin B chain

E9PS12

1.8

Inhibits the autoproteolytic cleavage of caspase-3, interacts with the pro-apoptotic proteins and prevents translocation to mitochondria

Promotes anti-apoptosis

34,35

Inhibits P53 dependent apoptosis by inhibiting Ras activation, blocks UVA cell apoptosis and binds to X-linked inhibitor of apoptosis to inhibit caspase

Promotes anti-apoptosis

36

Associated with transcriptional activation, regulates the Vascular Endothelial Growth Factor (VEGF) and confers VEGF resistance; Induces EGF and anchorage-independent growth through activation of the MEK/ERK pathway

Promotes tumorigenesis

37

2

Amine oxidase 3

K7EQZ5

3.4

Regulates myofibroblastic phenotype in a cancer-associated fibroblast

Promotes metastasis

38,39

3

Calponin 1

K7ENC5

3.0

Induces cytoskeleton changes that leads to EM

Promotes metastasis and invasion of tumor cell

40,41,42,43,44

4

Caveolin 1

C9JKI3

2.2

Regulates intrinsic, extrinsic apoptotic pathway proteins and downstream proteins; Cav-1 induced autophagy alteration influenced apoptosis

Promotes anti-apoptosis

45,46

Influences the levels of EMT (Epithelial to mesenchymal transition) associated markers, transcription factors, MMP and RhoGTPases; Participates in Cav1 dependent trafficking of integrins

Promotes invasion and migration

47,48,49

Endows anoikis resistance by inactivating caspase-8 and regulates the levels of metastasis-associated proteins like MT4-MMP, MMP9 and TLR4

Promotes metastasis

50,51

5

Collagen alpha-1

P02461

5.6

Induces mRNA level of MMP9 and regulates the target gene of Wnt/βcatenin pathways

Promotes invasion

52,53

6

Desmin

P17661

2.7

Activates Tumor stromal myofibroblasts and transforming growth factor (TGF)β that switches non-invasive to invasive cancer

Promotes angiogenesis

54

7

Fibrillin 1

P35555

3.8

Associates with TGFβ signalling which induces EMT and in turn regulates the expression of E-cadherin, beta-catenin and MMPs

Promotes growth, proliferation and invasion

55,56,57

8

Glyceraldehyde-3-phosphate dehydrogenase

P21695

3.1

Interacts with Sp1 and enhances the expression of SNAIL, a transcriptional inducer of EMT

Promotes invasion and metastasis

58

9

Heat shock protein gene 6

K7EP04

2.2

Chaperone focal adhesion kinase, integrin linked kinase and the receptor tyrosine kinases ErbB2 and MET

Promotes metastasis

59,60

Induces epithelial-mesenchymal transition, in which cells switch from a compact shape to a spindle shape

Increases cell motility

59,61

10

Laminin subunit alpha 4

Q16363

2.1

Involved in mitogen-activated protein kinases (MAPK) cascades and dual-specificity phosphatases in lamininsignaling in human melanoma cells

Promotes tumor progression, tumor invasion, metastasis

62,63

11

Membrane primary amine oxidase

Q16853

3.3

MAOA stabilizes HIF1α, activates the VEGF-A/NRP1 system, and induces expression of TWIST1, an EMT master transcription factor that participates in EMT promotion

Promotes migration, proliferation and invasion

64

12

Microfibril-associated glycoprotein 4

K7ES70

2.6

Inhibits Notch1 signaling and interacts with Jagged1

Promotes angiogenesis

65

Interacts with αvβ3 integrin receptor

Promotes tumor cell motility and survival

66

13

Myosin-11

P35749

3.0

Link to actin filaments

Promotes breast cancer motility

67

Response to impaired p53, cell adhesion inhibition, protrusion formation

Breast tumor progression

68

14

Perilipin-1

O60240

3.0

Regulates lipid network of fatty acid synthase (FASN) and sterol regulatory element-binding protein (SREBP) family

Promotes angiogenesis and metastasis in breast cancer

69

15

Redox-regulatory protein FAM213A

Q9BRX8

1.8

miR-211 and FAM213A represes TCF12(transcprition factor 12)

Promotes oncogenesis

70

16

Transgelin

K7ERK4

3

Associates with TGFβ/Smad-3 

Promotes invasion

71,72,73

Regulates the production of MMP2

Promotes metastasis

72,73