An epithelial GPR35 isoform supports tumor‐associated transcriptional and metabolic phenotypes

FEBS Letters 2026 Open access

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Authors: Jørgen D. Rønneberg, Martine Hjeltnes, Josephine Krieger, Joshua E. Elias, Maria Stensland, Kristian Holm, Xiaojun Jiang, Chuki Khangsar, Tuula A. Nyman, Arthur Kaser, Johannes R. Hov, Tom H. Karlsen
+3 more Nicole C. Kaneider, Frode L. Jahnsen, Georg Schneditz
DOI: 10.1002/1873-3468.70423
Cited by: 1
References: 42

Abstract

G protein-coupled receptor 35 (GPR35) has been implicated in cancer, but the functional roles of its isoforms remain unresolved. Here, we characterize GPR35-long, an N-terminally extended epithelial isoform selectively enriched in colorectal cancer and cholangiocarcinoma. Mass spectrometry and immunohistochemistry confirmed GPR35-long protein expression in tumor cells. Functional analyses revealed that GPR35-long supports tumor-associated transcriptional programs, enhances cellular ATP production, and exhibits increased constitutive and ligand-induced beta-arrestin signaling. These phenotypes were selectively suppressed by the inverse agonist CID-2745687, identifying GPR35-long as a functionally distinct isoform with selective pharmacological sensitivity in tumor cells.

Fields of Study & Subjects

Receptor Mechanisms and Signaling Protein Kinase Regulation and GTPase Signaling Estrogen and related hormone effects

Publication details

Journal / source
FEBS Letters
Publisher
Wiley
Volume
600
Issue
19
Pages
2876-2898
Publication date
1 August 2026
Language
EN