CDB25:0003702 GREM1 — FGFR1

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

Title

Journal:; Year Published:

Abstract

Gremlin1 is a therapeutically targetable FGFR1 ligand that regulates lineage plasticity and castration resistance in prostate cancer.

Nature cancer, 2022; PubMed, Homo sapiens GREM1 — Homo sapiens FGFR1

ABSTRACT: Among the greatest hurdles in clinical management of prostate cancer (PCa) are the progression to lethal castration-resistant prostate cancer (CRPC) and the lack of suitable targeted therapies for advanced disease. Here we identify Gremlin1 as a ligand for fibroblast growth factor receptor 1 (FGFR1), which promotes lineage plasticity and drives castration resistance. Importantly, we generate a specific anti-Gremlin1 therapeutic antibody and demonstrate synergistic effect with androgen deprivation therapy (ADT) in CRPC. GREM1 transcription is suppressed by androgen receptor (AR) and released following ADT. We show that Gremlin1 binds to FGFR1 and activates downstream MAPK signaling. Gremlin1 interacts with FGFR1 differently to its canonical ligand FGF1, as revealed through protein structure docking and mutagenesis experiments. Altogether, our data indicate Gremlin1 as a promising candidate therapeutic target for CRPC.

Basic Information on GREM1

Ligand Name: gremlin 1, DAN family BMP antagonist

Other Symbols: CKTSF1B1, CRAC1, DRM, gremlin, DAND2, HMPS

Ligand Location: secreted based on perplexity, uniprot

HGNC Gene Symbol Report: GREM1

GeneCards: GREM1

HGNC Gene Group: DAN family

Functional Annotations for GREM1

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 GREM1

GREM1 — KDR

Basic Information on FGFR1

Receptor Name: fibroblast growth factor receptor 1

Other Symbols: FLT2, KAL2, H2, H3, H4, H5, CEK, FLG, BFGFR, N-SAM, CD331

Receptor Location: cell membrane based on perplexity, uniprot

HGNC Gene Symbol Report: FGFR1

GeneCards: FGFR1

HGNC Gene Group: Receptor kinases, CD molecules, Immunoglobulin superfamily domain containing

Functional Annotations for FGFR1

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 FGFR1

FGF10 — FGFR1 ・ FGF16 — FGFR1 ・ FGF17 — FGFR1 ・ FGF18 — FGFR1 ・ FGF19 — FGFR1 ・ FGF1 — FGFR1 ・ FGF23 — FGFR1 ・ FGF2 — FGFR1 ・ FGF3 — FGFR1 ・ FGF4 — FGFR1 ・ FGF5 — FGFR1 ・ FGF6 — FGFR1 ・ FGF7 — FGFR1 ・ FGF8 — FGFR1 ・ FGF9 — FGFR1 ・ ANOS1 — FGFR1 ・ NCAM1 — FGFR1 ・ FGF20 — FGFR1 ・ FGF22 — FGFR1 ・ CCN2 — FGFR1 ・ CDH1 — FGFR1 ・ FAM3B — FGFR1 ・ FGF21 — FGFR1 ・ L1CAM — FGFR1 ・ MMP2 — FGFR1 ・ NECTIN1 — FGFR1 ・ PF4 — FGFR1