Evidence map›Paper›PMID 41865639›Full record

ArticleNeoplasia (New York, N.Y.)2026

PRAS40 activates the IRE1α-XBP-1-mediated unfolded protein response to exacerbate colorectal cancer by enhancing ST6Gal1-dependent α-2, 6 sialylation of GRP78.

Hongming Teng, Yuxin Guo, Xinran Chen, Anlian Fan, Chengfei Zhang, Ting Zhang, Yuanyuan Luo, Lin Huang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neoplasia (New York, N.Y.), 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

8 authors.

Hongming TengDepartment of Pathophysiology, College of Basic Medical Sciences, Dalian Medical University, 9 South Lvshun Road, Dalian, Liaoning 116044, PR China; Liaoning Provincial Key Laboratory of Medical Cellular and Molecular Biology, 9 South Lvshun Road, Dalian, Liaoning 116044, PR China.
Yuxin GuoDepartment of Pathophysiology, College of Basic Medical Sciences, Dalian Medical University, 9 South Lvshun Road, Dalian, Liaoning 116044, PR China.
Xinran ChenDepartment of Pathophysiology, College of Basic Medical Sciences, Dalian Medical University, 9 South Lvshun Road, Dalian, Liaoning 116044, PR China.
Anlian FanDepartment of Pathophysiology, College of Basic Medical Sciences, Dalian Medical University, 9 South Lvshun Road, Dalian, Liaoning 116044, PR China.
Chengfei ZhangDepartment of Pathophysiology, College of Basic Medical Sciences, Dalian Medical University, 9 South Lvshun Road, Dalian, Liaoning 116044, PR China.
Ting ZhangDepartment of Pathophysiology, College of Basic Medical Sciences, Dalian Medical University, 9 South Lvshun Road, Dalian, Liaoning 116044, PR China; Liaoning Provincial Key Laboratory of Medical Cellular and Molecular Biology, 9 South Lvshun Road, Dalian, Liaoning 116044, PR China.
Yuanyuan LuoDepartment of Pathophysiology, College of Basic Medical Sciences, Dalian Medical University, 9 South Lvshun Road, Dalian, Liaoning 116044, PR China; Liaoning Provincial Key Laboratory of Medical Cellular and Molecular Biology, 9 South Lvshun Road, Dalian, Liaoning 116044, PR China.
Lin HuangDepartment of Pathophysiology, College of Basic Medical Sciences, Dalian Medical University, 9 South Lvshun Road, Dalian, Liaoning 116044, PR China; Liaoning Provincial Key Laboratory of Medical Cellular and Molecular Biology, 9 South Lvshun Road, Dalian, Liaoning 116044, PR China. Electronic address: lhuang@dmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Colorectal cancer (CRC) progression could be fueled by the activation of the unfolded protein response (UPR) triggered by endoplasmic reticulum (ER) stress. The proline-rich Akt1 substrate of 40 kDa (PRAS40) is implicated in cancer progression, but its role in the UPR remains unclear. Herein, we demonstrate that PRAS40 promotes the inositol-requiring enzyme 1α (IRE1α)-X-box binding protein 1 (XBP1) axis-dependent UPR in driving CRC progression. Mechanistically, PRAS40 interacts with ER chaperone glucose-regulated protein 78 (GRP78) and enhances its N-glycosylation. Moreover, PRAS40 improves the interaction between GRP78 and ST6 β-galactoside α-2, 6-sialyltransferase 1 (ST6Gal1), leading to increased α-2, 6-sialylation of GRP78 and the UPR triggered by ER stress. Furthermore, we identified the natural compound β-sitosterol as a novel ST6Gal1 inhibitor, which attenuated PRAS40-triggered tumor growth. Collectively, these findings unveil a PRAS40-ST6Gal1-GRP78 axis that drives CRC progression through activating the IRE1α-XBP-1-mediated UPR and nominate ST6Gal1 as a promising therapeutic target.

Indexed as

Adaptor Proteins, Signal TransducingColorectal NeoplasmsEndoribonucleasesHeat-Shock ProteinsProtein Serine-Threonine KinasesSialyltransferasesUnfolded Protein ResponseX-Box Binding Protein 1AnimalsAntigens, CDbeta-D-Galactoside alpha 2-6-SialyltransferaseCell Line, TumorEndoplasmic Reticulum Chaperone BiPEndoplasmic Reticulum StressHumansMiceAdaptor Proteins, Signal TransducingAntigens, CDbeta-D-Galactoside alpha 2-6-SialyltransferaseEndoplasmic Reticulum Chaperone BiPEndoribonucleasesERN1 protein, humanHeat-Shock ProteinsHSPA5 protein, humanHspa5 protein, mouseProtein Serine-Threonine KinasesSialyltransferasesST6GAL1 protein, humanX-Box Binding Protein 1XBP1 protein, humanColorectal cancerEndoplasmic reticulum stressGRP78PRAS40The unfolded protein response

Identifiers

PMID41865639
PMCPMC13020080

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.