Evidence map›Paper›PMID 39513392›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

The Antipsychotic Drug Aripiprazole Suppresses Colorectal Cancer by Targeting LAMP2a to Induce RNH1/miR-99a/mTOR-Mediated Autophagy and Apoptosis.

Hui-Fang Hu, Jia-Ying Fu, Lei Han, Gui-Bin Gao, Wei-Xia Zhang, Si-Ming Yu, Nan Li, Yang-Jia Li, Yi-Fan Lu, Xiao-Feng Ding and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

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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

13 authors.

Hui-Fang HuMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.ORCID 0009-0001-0223-5044
Jia-Ying FuMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Lei HanInstitute of Biomedicine and National Engineering Research Center of Genetic Medicine and Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, National Engineering Research Centre of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Gui-Bin GaoMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Wei-Xia ZhangMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Si-Ming YuInstitute of Biomedicine and National Engineering Research Center of Genetic Medicine and Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, National Engineering Research Centre of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Nan LiMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Yang-Jia LiMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Yi-Fan LuMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Xiao-Feng DingMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Yun-Long PanThe First Affiliated Hospital of Jinan University and MOE Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, 510632, China.
Yang WangMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Qing-Yu HeMOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.

Funding

China Postdoctoral Science Foundation 2021M701418Fundamental Research Funds for the Central Universities 21623207Guangdong Natural Science Research Grant 2021A1515111126Guangdong Natural Science Research Grant 2023A1515010324National Key R&D Program of China 2020YFE0202200National Key R&D Program of China 2022YFA1304600National Natural Science Foundation of China 82202842Science and Technology Projects in Guangzhou 2024A04J4018Young Talent Support Project of Guangzhou Association for Science and Technology QT2024-003
6 · The paper itself

Abstract

The mammalian target of rapamycin (mTOR) is a critical signaling hub for sustaining cancer survival. Targeting mTOR and inducing autophagic cell death downstream of it represent promising therapeutic strategies for cancer prevention. A US Food and Drug Administration-approved drug library containing 616 small molecules is used to screen anticancer drugs against colorectal cancer (CRC) cells that rely on mTOR. This led to the identification of an antipsychotic drug aripiprazole, which significantly induced mTOR inhibition and autophagic apoptosis in CRC, in vitro and in vivo. The use of drug affinity response target stability identified lysosome-associated membrane protein 2A (LAMP2a) as a direct target of aripiprazole. LAMP2a-deficient CRC cells are refractory to aripiprazole. High LAMP2a expression is associated with poor survival of patients with CRC and negatively correlated with expression of ribonuclease inhibitor 1 (RNH1), which is later confirmed as a novel substrate of LAMP2a. Mechanistically, aripiprazole bound to the Lys401-His404 of LAMP2a and repressed its activity, subsequently inactivating RNH1/miR-99a/mTOR signaling and inducing autophagy-mediated apoptosis, thereby suppressing tumorigenesis. Liposome-mediated delivery of aripiprazole in combination with fluorouracil elicited superior therapeutic benefits in CRC, as compared to single treatments, thereby highlighting that aripiprazole may be repurposed as a novel therapeutic agent for CRC treatment.

Indexed as

Antipsychotic AgentsApoptosisAripiprazoleAutophagyColorectal NeoplasmsLysosomal-Associated Membrane Protein 2MicroRNAsTOR Serine-Threonine KinasesAnimalsCell Line, TumorDisease Models, AnimalHumansMiceMice, NudeSignal TransductionAntipsychotic AgentsAripiprazoleLAMP2 protein, humanLysosomal-Associated Membrane Protein 2MicroRNAsMTOR protein, humanTOR Serine-Threonine Kinases5‐FUaripiprazoleautophagyLAMP2amTOR

Identifiers

PMID39513392
PMCPMC11672294

What OpenQuestion holds

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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.