Evidence map›Paper›PMID 41685236›Full record

ReviewFrontiers in endocrinology2026

Purinergic signal transduction and metabolic regulation by ENTPD5 and ENTPD6.

Yihang Qi, Xuefei Li, Xinyu Song, Wenyi Wei, Ionita Ghiran, Simon C Robson

Abstract readReview
In one paragraph

Review in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Yihang Qi *Center for Inflammation Research, Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Xuefei Li *Center for Inflammation Research, Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Xinyu SongCenter for Inflammation Research, Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Wenyi WeiDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Ionita GhiranCenter for Inflammation Research, Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Simon C RobsonCenter for Inflammation Research, Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

ENTPD5 and ENTPD6 are members of the CD39-ectonucleoside triphosphate diphosphohydrolase (CD39-ENTPD) family, which play an important role in modulating the purinergic signaling pathway. Most of the knowledge in this area has been obtained by studying CD39/ENTPD1, the prototype member of this family, and evaluating the translational potential by either treating inflammation directly with recombinant proteins or by using antagonists to elicit immune responses in cancer. ENTPD5 and ENTPD6, "orphan-type" ectonucleotidases, are understudied to date, although both are expressed at high levels in various tissues, where they appear involved in regulating signal transduction, cellular energy, and metabolism. ENTPD5 is abnormally overexpressed in several types of malignancies, including prostate, liver, lung, and ovarian cancers. ENTPD5 appears to promote protein glycosylation and folding in part by regulating UDP and UMP levels, thereby enhancing the survival and proliferation of somatic or cancer cells. As such, ENTPD5 has been considered a potential proto-oncogene and a therapeutic target in cancer treatment. In contrast, despite comparable functionality, the related ENTPD6 shows relatively stable expression across tissues in both normal and pathological conditions, with specific roles in cancer yet unclear. This review provides a comprehensive overview of these two understudied ectoenzymes, detailing their shared molecular structures and control of purinergic signal transduction. In addition, we explore different patterns of tissue and organelle expression of these ecto-enzymes and propose relevance to the modulation of cellular metabolism, as would be important in cancer. We review the sometimes conflicting evidence from experimental animal models and propose potential future clinical applications. This review offers insights into the roles of this distinct duo of ENTPD family members to support future basic and translational research in this field.

Indexed as

ApyraseNeoplasmsPurinesSignal TransductionAnimalsHumansOncogene ProteinsProto-Oncogene MasPyrophosphatasesApyraseENTPD5 protein, humanMAS1 protein, humanOncogene ProteinsProto-Oncogene MasPurinesPyrophosphatasescancerCD39L2CD39L4ectonucleoside triphosphate diphosphohydrolase 5ectonucleoside triphosphate diphosphohydrolase 6ENTPD5ENTPD6purinergic signaling pathway

Identifiers

PMID41685236
PMCPMC12890697

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.