CDB25:0003877 LGALS3 — ITGB3

Experimentally validated in Human; Orthology-inferred in Mouse, Rat, Frog, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep

Title

Journal:; Year Published:

Abstract

Galectin-3, a Druggable Vulnerability for KRAS-Addicted Cancers.

Cancer discovery, 2017; PubMed, Homo sapiens LGALS3 — Homo sapiens ITGB3

ABSTRACT: Identifying the molecular basis for cancer cell dependence on oncogenes such as KRAS can provide new opportunities to target these addictions. Here, we identify a novel role for the carbohydrate-binding protein galectin-3 as a lynchpin for KRAS dependence. By directly binding to the cell surface receptor integrin αvβ3, galectin-3 gives rise to KRAS addiction by enabling multiple functions of KRAS in anchorage-independent cells, including formation of macropinosomes that facilitate nutrient uptake and ability to maintain redox balance. Disrupting αvβ3/galectin-3 binding with a clinically active drug prevents their association with mutant KRAS, thereby suppressing macropinocytosis while increasing reactive oxygen species to eradicate αvβ3-expressing KRAS-mutant lung and pancreatic cancer patient-derived xenografts and spontaneous tumors in mice. Our work reveals galectin-3 as a druggable target for KRAS-addicted lung and pancreas cancers, and indicates integrin αvβ3 as a biomarker to identify susceptible tumors.Significance: There is a significant unmet need for therapies targeting KRAS-mutant cancers. Here, we identify integrin αvβ3 as a biomarker to identify mutant KRAS-addicted tumors that are highly sensitive to inhibition of galectin-3, a glycoprotein that binds to integrin αvβ3 to promote KRAS-mediated activation of AKT. Cancer Discov; 7(12); 1464-79. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 1355.

Basic Information on LGALS3

Ligand Name: galectin 3

Other Symbols: LGALS2, MAC-2, GALIG

Ligand Location: secreted based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: LGALS3

GeneCards: LGALS3

HGNC Gene Group: Receptor ligands, Galectins

Functional Annotations for LGALS3

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 LGALS3

LGALS3 — LAG3 ・ LGALS3 — CDH5 ・ LGALS3 — ENG ・ LGALS3 — IL13RA2 ・ LGALS3 — ITGB1 ・ LGALS3 — ITGB4 ・ LGALS3 — MCAM ・ LGALS3 — MERTK ・ LGALS3 — MUC1 ・ LGALS3 — PECAM1 ・ LGALS3 — TYRO3

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 ・ IL32 — 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 ・ NRG1 — ITGB3 ・ PECAM1 — ITGB3 ・ PLAUR — ITGB3 ・ POSTN — ITGB3 ・ PTN — ITGB3 ・ RELN — ITGB3 ・ THY1 — ITGB3 ・ VWF — ITGB3