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

IF 3 4区生物学 Q1 Biochemistry, Genetics and Molecular Biology

FEBS Letters Pub Date : 2026-10-12 Epub Date: 2026-08-01 DOI:10.1002/1873-3468.70423

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, Nicole C. Kaneider, Frode L. Jahnsen, Georg Schneditz

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引用次数: 0

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.

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上皮GPR35亚型支持肿瘤相关的转录和代谢表型。

G蛋白偶联受体35 （GPR35）与癌症有关，但其异构体的功能作用尚不清楚。在这里，我们表征了GPR35-long，这是一种在结直肠癌和胆管癌中选择性富集的n端延伸上皮异构体。质谱和免疫组化证实肿瘤细胞中表达GPR35-long蛋白。功能分析显示，GPR35-long支持肿瘤相关的转录程序，增强细胞ATP的产生，并表现出增加的组成和配体诱导的β -阻滞蛋白信号传导。这些表型被反向激动剂CID-2745687选择性抑制，鉴定出GPR35-long是肿瘤细胞中具有选择性药理学敏感性的功能独特的亚型。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

FEBS Letters 生物-生化与分子生物学

CiteScore

7.00

自引率

2.90%

发文量

303

审稿时长

1.0 months

期刊介绍： FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.