⮝ Full datasets listing
PXD077367
PXD077367 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | High-potassium microenvironment drives KCNMA1⁺ CAF-mediated progression of perineural invasion-positive colorectal cancer via the CCL11/CCR5 axis |
| Description | Perineural invasion (PNI) is an established independent prognostic risk factor in colorectal cancer (CRC) and is significantly associated with resistance to immunotherapy; however, the mechanisms underlying cellular communication remain inadequately understood. Here, using single-nucleus RNA sequencing, we identified a previously uncharacterized KCNMA1⁺ cancer-associated fibroblast (CAF) subpopulation specifically enriched in PNI-positive CRC. Analysis of multicenter clinical cohorts confirmed that KCNMA1⁺CAFs correlate with PNI status and poor survival. Functionally, this subset of CAFs induces pro-tumor M2-type macrophage polarization via paracrine CCL11, thereby remodeling the immunosuppressive tumor microenvironment and facilitating tumor progression. In terms of the induction mechanism, tumor infiltration into neural tissues induces extensive cellular necrosis within the PNI niche, creating a potassium-rich (K+-rich) microenvironment that drives the phenotypic transition of CAFs toward the KCNMA1⁺ subtype. Pharmacological inhibition of the CCL11-CCR5 axis effectively attenuates KCNMA1⁺CAF-mediated immunosuppression and sensitizes PNI-positive tumors to anti-PD-1 therapy. Collectively, this study elucidates the critical role of PNI-induced ionic microenvironment remodeling in promoting CAF heterogeneity and suggests potential combination therapeutic strategies for patients with PNI-positive CRC. |
| HostingRepository | iProX |
| AnnounceDate | 2026-04-20 |
| AnnouncementXML | Submission_2026-04-19_20:09:31.625.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Zhixuan Wu |
| SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Orbitrap Exploris 240 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2026-04-19 20:09:11 | ID requested | |
| ⏵ 1 | 2026-04-19 20:09:32 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: KCNMA1⁺ CAF, perineural invasion, colorectal cancer, high-potassium microenvironment, CCL11/CCR5 |
Contact List
| Zhangfa Song | |
|---|---|
| contact affiliation | Sir Run Run Shaw Hospital, Zhejiang University School of Medicine |
| contact email | songzhangfa@zju.edu.cn |
| lab head | |
| Zhixuan Wu | |
| contact affiliation | Sir Run Run Shaw Hospital, Zhejiang University School of Medicine |
| contact email | wuzhixuan0922@163.com |
| dataset submitter | |
Full Dataset Link List
| iProX dataset URI |
