# Latest advances on the role of P2X Receptors in colorectal inflammation and cancer

**Authors:** Luigia Ruo, Federica Fortuna, Marianna Grignolo, Anna Pegoraro, Elena Adinolfi

PMC · DOI: 10.1007/s11302-026-10146-6 · 2026-03-18

## TL;DR

This review explores how P2X receptors contribute to colon inflammation and cancer, and discusses potential targeted therapies.

## Contribution

The paper provides a comprehensive overview of P2X receptor roles in colonic diseases and highlights personalized therapeutic strategies.

## Key findings

- P2X receptors are involved in intestinal inflammation and tumor-promoting microenvironments.
- Dysregulated P2X signaling affects immune cell activation and visceral hypersensitivity.
- Therapeutic strategies targeting P2X receptors are emerging, emphasizing personalized approaches.

## Abstract

Extracellular adenosine triphosphate (eATP) is a hallmark of inflammatory and tumor-associated microenvironments, where it functions as a key extracellular signalling molecule through activation of purinergic receptors. In the gastrointestinal tract, and particularly in the colon, eATP-mediated signalling regulates epithelial barrier function, neuroimmune interactions, and immune responses. P2X receptors, a family of eATP-gated ion channels, are differentially expressed across epithelial, neuronal, and immune cell populations and are increasingly recognized as contributors to colonic pathophysiology. This review summarizes current evidence on the roles of P2X receptors in inflammatory bowel disease and colon carcinoma, highlighting their involvement in intestinal inflammation, visceral hypersensitivity, immune cell activation, and tumor-associated processes. We discuss how dysregulated P2X receptor signalling contributes to chronic inflammation and supports a tumor-promoting microenvironment, while also emphasizing the context- and cell-type-specific nature of these responses. Finally, we outline emerging therapeutic strategies targeting P2X receptors and underscore the importance of personalized approaches based on receptor expression patterns within the colonic tissue.

## Linked entities

- **Chemicals:** adenosine triphosphate (PubChem CID 5957)
- **Diseases:** inflammatory bowel disease (MONDO:0005265), colon carcinoma (MONDO:0002032)

## Full-text entities

- **Genes:** Gjd2 (gap junction protein, delta 2) [NCBI Gene 14617] {aka Cxns, Gja9, connexin36, cx36}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, Nt5e (5' nucleotidase, ecto) [NCBI Gene 23959] {aka 2210401F01Rik, 5'-NT, CD73, NT, Nt5, eNT}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, Ccl5 (C-C motif chemokine ligand 5) [NCBI Gene 20304] {aka MuRantes, RANTES, SISd, Scya5, TCP228}, Il17a (interleukin 17A) [NCBI Gene 16171] {aka Ctla-8, Ctla8, IL-17, IL-17A, Il17}, P2rx7 (purinergic receptor P2X, ligand-gated ion channel, 7) [NCBI Gene 18439] {aka P2X(7), P2X7R}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Pecam1 (platelet/endothelial cell adhesion molecule 1) [NCBI Gene 18613] {aka Cd31, PECAM-1, Pecam}, Il23a (interleukin 23, alpha subunit p19) [NCBI Gene 83430] {aka IL-23, p19}, Entpd8 (ectonucleoside triphosphate diphosphohydrolase 8) [NCBI Gene 72090], Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Csf3 (colony stimulating factor 3 (granulocyte)) [NCBI Gene 12985] {aka Csfg, G-CSF, MGI-IG}, Gsk3b (glycogen synthase kinase 3 beta) [NCBI Gene 56637] {aka 7330414F15Rik, 8430431H08Rik, GSK-3, GSK-3beta, GSK3}, Ocln (occludin) [NCBI Gene 18260] {aka Ocl}, Cd274 (CD274 antigen) [NCBI Gene 60533] {aka A530045L16Rik, B7h1, Pdcd1l1, Pdcd1lg1, Pdl1}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Entpd1 (ectonucleoside triphosphate diphosphohydrolase 1) [NCBI Gene 12495] {aka 2610206B08Rik, ATP-DPH, Cd39, E130009M23Rik, NTPDase-1}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Apc (APC, WNT signaling pathway regulator) [NCBI Gene 11789] {aka CC1, Min, mAPC}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, P2rx1 (purinergic receptor P2X, ligand-gated ion channel, 1) [NCBI Gene 18436] {aka P2x, Pdcd3, RP-2}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}
- **Diseases:** blood loss (MESH:D016063), anemia (MESH:D000740), colitis (MESH:D003092), necrotic (MESH:D009336), gastric cancer (MESH:D013274), periodontitis (MESH:D010518), gut dysbiosis (MESH:D064806), colon carcinoma (MESH:D003110), pain (MESH:D010146), breast, prostate, hepatic, and colon carcinomas (MESH:D011472), thrombosis (MESH:D013927), colon inflammation (MESH:D007249), visceral hypersensitivity (MESH:D004342), visceral pain (MESH:D059265), colon cancer (MESH:D015179), neuronal death (MESH:D009410), colonic and hepatic damage (MESH:D003108), gastrointestinal disorders (MESH:D005767), bleeding (MESH:D006470), postoperative ileus (MESH:D045823), Abdominal pain (MESH:D015746), sarcoma (MESH:D012509), neuroimmune dysregulation (MESH:D021081), IBD (MESH:D015212), CRC (MESH:D009369), gliosis (MESH:D005911), Crohn's (MESH:D003424), ulcerative colitis (MESH:D003093), tissue damage (MESH:D017695), fibrosis (MESH:D005355), intestinal (MESH:D007410), metastasis (MESH:D009362)
- **Chemicals:** adenosine (MESH:D000241), AZ10606120 (MESH:C000602458), ATP (MESH:D000255), LY294002 (MESH:C085911), alcohol (MESH:D000438), nucleotides (MESH:D009711), dexamethasone (MESH:D003907), ROS (MESH:D017382), 2,4,6-Trinitrobenzene Sulphonic Acid (-), A438079 (MESH:C523668), glycogen (MESH:D006003), 2,4-Dinitrobenzene Sulfonic Acid (MESH:C001073), A-317491 (MESH:C470346), NP-1815-PX (MESH:C000627125)
- **Species:** Homo sapiens (human, species) [taxon 9606], Porphyromonas gingivalis (species) [taxon 837], Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Mutations:** A2A
- **Cell lines:** CT26 — Mus musculus (Mouse), Mouse colon adenocarcinoma, Cancer cell line (CVCL_7254), HCT116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), SW620 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0547)

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC13000090/full.md

---
Source: https://tomesphere.com/paper/PMC13000090