Evidence map›Paper›PMID 42776282›Full record

ArticleApoptosis : an international journal on programmed cell death2026

Targeting LAMP2 synergizes with gemcitabine to inhibit bladder cancer progression via modulating STING degradation and regulating macrophage phenotypes.

Yue Lv, Qiang Yin, Wuheng Li, Leihong Deng, Jiasheng Liu, Haolong Lv, Peng Zhang, Yihang Qiu, Difeng Guo, Rui Tao and 4 more

Abstract read
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In one paragraph

Article in Apoptosis : an international journal on programmed cell death, 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

14 authors.

Yue LvDepartment of Urology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150000, Heilongjiang, China.
Qiang YinDepartment of Urology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150000, Heilongjiang, China.
Wuheng LiDepartment of Urology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150000, Heilongjiang, China.
Leihong DengDepartment of Ultrasound Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
Jiasheng LiuDepartment of Urology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150000, Heilongjiang, China.
Haolong LvDepartment of Urology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150000, Heilongjiang, China.
Peng ZhangDepartment of Urology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150000, Heilongjiang, China.
Yihang QiuDepartment of Urology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150000, Heilongjiang, China.
Difeng GuoDepartment of Urology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150000, Heilongjiang, China.
Rui TaoDepartment of Urology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150000, Heilongjiang, China.
Xiuguo GanDepartment of Urology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150000, Heilongjiang, China. ganxiuguo@qq.com.
Fanghua XuDepartment of Pathology, Ping Xiang People's Hospital, Pingxiang Economic and Technological Development District, No. 8, Wugong Mountain Avenue, Development Zone, Ping Xiang, 337000, Jiangxi, China. jiangxiren111@126.com.
Zan LiuDepartment of Urology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150000, Heilongjiang, China. Liuzan@hrbmu.edu.cn.
Yongquan WangDepartment of Urology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150000, Heilongjiang, China. yongquanwang@hrbmu.edu.cn.

Funding

the China Primary Healthcare Foundation 2021IIT002
6 · The paper itself

Abstract

Bladder cancer (BLCA) is an aggressive malignancy characterized by metastasis and drug resistance, creating an urgent demand for novel therapeutic targets. The lysosomal protein LAMP2 acts as a key oncogenic driver in BLCA and modulates the degradation of STING. As reported in prior studies, mechanistically, p62-mediated macroautophagy and HSC70-dependent chaperone-mediated autophagy (CMA) facilitate STING degradation. LAMP2 increases STING ubiquitination, leading to its lysosomal degradation in BLCA. Moreover, LAMP2 knockdown suppresses BLCA cell proliferation and migration. In our experimental systems, it also induces M1-type tumor-associated macrophages (TAMs) polarization and reduces TAM infiltration. RNF5 and TRIM56 are known to mediate K48/K63-linked ubiquitination of STING. Here, we demonstrate LAMP2 modulates this ubiquitination pattern in BLCA. Via virtual screening, we discover MRGPRX4 modulator-2 (Mm-2), a LAMP2-binding small molecule with anti-tumor activity against BLCA. Combined with gemcitabine (GEM), Mm-2 blocks autophagic flux and activates STING signaling. It also alters TAM phenotypes in our in vitro and in vivo models. The LAMP2-STING-TAMs axis shows potential as a therapeutic target for modulating the tumor immune microenvironment (TME) and affecting drug response in BLCA.

Indexed as

DeoxycytidineLysosomal-Associated Membrane Protein 2MacrophagesMembrane ProteinsUrinary Bladder NeoplasmsAnimalsAutophagyCell Line, TumorCell ProliferationcGAS-STING Signaling PathwayDisease ProgressionFemaleGemcitabineHumansMicePhenotypeDeoxycytidineGemcitabineLAMP2 protein, humanLysosomal-Associated Membrane Protein 2Membrane ProteinsSTING1 protein, humanSTING ProteinAutophagyBLCALAMP2MacrophageSTING

Identifiers

PMID42776282

What Socratic holds

Textmetadata
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.