CDB20:0002792 IL32 — ITGB3

Experimentally validated in Human; Orthology-inferred in Dog, Cow, Chimp, Horse

Title

Journal:; Year Published:

Abstract

Cancer-associated fibroblast (CAF)-derived IL32 promotes breast cancer cell invasion and metastasis via integrin β3-p38 MAPK signalling.

Cancer letters, 2019; PubMed, Homo sapiens IL32 — Homo sapiens ITGB3

ABSTRACT: Metastasis is the leading cause of breast cancer-related deaths. Cancer-associated fibroblasts (CAFs), the predominant stromal cell type in the breast tumour microenvironment, may contribute to cancer progression through interaction with tumour cells. Nonetheless, little is known about the details of the underlying mechanism. Here we found that interaction of interleukin 32 (IL32) with integrin β3 (encoded by ITGB3; a member of the integrin family) mediating the cross-talk between CAFs and breast cancer cells plays a crucial role in CAF-induced breast tumour invasiveness. IL32, an 'RGD' motif-containing cytokine, was found to be abundantly expressed in CAFs. Integrin β3 turned out to be up-regulated in breast cancer cells during epithelial-mesenchymal transition (EMT). CAF-derived IL32 specifically bound to integrin β3 through the RGD motif, thus activating intracellular downstream p38 MAPK signalling in breast cancer cells. This signalling increased the expression of EMT markers (fibronectin, N-cadherin, and vimentin) and promoted tumour cell invasion. Counteracting IL32 activity, a knockdown of IL32 or integrin β3 led to specific inactivation of p38 MAPK signalling in tumour cells. Blockage of the p38 MAPK pathway also diminished IL32-induced expression of EMT markers and breast cancer cell invasion and metastasis. Thus, our data indicate that CAF-secreted IL32 promotes breast cancer cell invasion and metastasis via integrin β3-p38 MAPK signalling.

Basic Information on IL32

Ligand Name: interleukin 32

Other Symbols: NK4, TAIF, TAIFb, TAIFd

Ligand Location: secreted based on perplexity, uniprot

HGNC Gene Symbol Report: IL32

GeneCards: IL32

HGNC Gene Group: Receptor ligands: Interleukins

Functional Annotations for IL32

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for IL32

Basic Information on ITGB3

Receptor Name: integrin subunit beta 3

Other Symbols: GP3A, CD61, GPIIIa

Receptor Location: cell membrane based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: ITGB3

GeneCards: ITGB3

HGNC Gene Group: CD molecules, Integrins

Functional Annotations for ITGB3

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for ITGB3

ADAM15 — ITGB3 ・ ADAM23 — ITGB3 ・ ANGPTL3 — ITGB3 ・ CCN1 — ITGB3 ・ FBLN2 — ITGB3 ・ FBN1 — ITGB3 ・ FGA — ITGB3 ・ FN1 — ITGB3 ・ ICAM4 — ITGB3 ・ MFGE8 — ITGB3 ・ NID1 — ITGB3 ・ TGM2 — ITGB3 ・ THBS1 — ITGB3 ・ VTN — ITGB3 ・ COMP — ITGB3 ・ CX3CL1 — ITGB3 ・ CXCL12 — ITGB3 ・ EDIL3 — ITGB3 ・ PLA2G2A — ITGB3 ・ SPP1 — ITGB3 ・ TNC — ITGB3 ・ AZGP1 — ITGB3 ・ CCN3 — ITGB3 ・ CD40LG — ITGB3 ・ COL18A1 — ITGB3 ・ COL4A3 — ITGB3 ・ DMP1 — ITGB3 ・ EGFL7 — ITGB3 ・ FCER2 — ITGB3 ・ FGB — ITGB3 ・ FGF1 — ITGB3 ・ FGF2 — ITGB3 ・ FGG — ITGB3 ・ HMGB1 — ITGB3 ・ IBSP — ITGB3 ・ IGF1 — ITGB3 ・ IGF2 — ITGB3 ・ IL1B — ITGB3 ・ L1CAM — ITGB3 ・ LAMA4 — ITGB3 ・ LGALS3 — ITGB3 ・ NRG1 — ITGB3 ・ PECAM1 — ITGB3 ・ PLAUR — ITGB3 ・ POSTN — ITGB3 ・ PTN — ITGB3 ・ RELN — ITGB3 ・ THY1 — ITGB3 ・ VWF — ITGB3