Evidence map›Paper›PMID 32366480›Full record

ArticleCancer research2020

RETRACTED: Senescent Stromal Cells Promote Cancer Resistance through SIRT1 Loss-Potentiated Overproduction of Small Extracellular Vesicles.

Liu Han, Qilai Long, Shenjun Li, Qixia Xu, Boyi Zhang, Xuefeng Dou, Min Qian, Yannasittha Jiramongkol, Jianming Guo, Liu Cao and 4 more

RetractedOpen access · bronzeAbstract readCommentRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
4.3field-weighted citation impact, top 5% of its field
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

57 citing papers in PubMed, 98 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 9 institutions in 3 countries.

Liu Han *CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Qilai Long *Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
Shenjun LiNon-Clinical Research Department, RemeGen, Ltd. Yantai, Shandong, China.
Qixia XuInstitute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Boyi ZhangCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Xuefeng DouCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Min QianCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Yannasittha JiramongkolDepartment of Surgery and Cancer, Imperial College London, London, United Kingdom.ORCID 0000-0003-1824-4313
Jianming GuoDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
Liu CaoKey Laboratory of Medical Cell Biology, China Medical University, Shenyang, China.
Y Eugene ChinInstitute of Biology and Medical Sciences, Soochow University Medical College, Suzhou, Jiangsu, China.
Eric W-F LamDepartment of Surgery and Cancer, Imperial College London, London, United Kingdom.ORCID 0000-0003-1274-3576
Jing JiangDepartment of Pharmacology, Binzhou Medical University, Yantai, Shandong, China.
Yu SunCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. sunyu@sibs.ac.cn.
Shanghai Institute of Nutrition and Health · CNFudan University · CNImperial College London · GBBinzhou University · CNChina Medical University · CNShandong Institute of Business and Technology · CNShanghai Institutes for Biological Sciences · CNSoochow University · CNUniversity of Washington · US

Funding

Biotechnology and Biological Sciences Research Council BBS/B/03785Cancer Research UK 12011Medical Research Council MR/N012097/1
6 · The paper itself

Abstract

Cellular senescence is a potent tumor-suppressive program that prevents neoplastic events. Paradoxically, senescent cells develop an inflammatory secretome, termed the senescence-associated secretory phenotype, which is implicated in age-related pathologies including cancer. Here, we report that senescent cells actively synthesize and release small extracellular vesicles (sEV) with a distinctive size distribution. Mechanistically, SIRT1 loss supported accelerated sEV production despite enhanced proteome-wide ubiquitination, a process correlated with ATP6V1A downregulation and defective lysosomal acidification. Once released, senescent stromal sEVs significantly altered the expression profile of recipient cancer cells and enhanced their aggressiveness, specifically drug resistance mediated by expression of ATP-binding cassette subfamily B member 4 (ABCB4). Targeting SIRT1 with agonist SRT2104 prevented development of cancer resistance by restraining sEV production by senescent stromal cells. In clinical oncology, sEVs in peripheral blood of posttreatment cancer patients were readily detectable by routine biotechniques, presenting an exploitable biomarker to monitor therapeutic efficacy and predict long-term outcome. Together, this study identifies a distinct mechanism supporting pathologic activities of senescent cells and provides a potent avenue to circumvent advanced human malignancies by cotargeting cancer cells and their surrounding microenvironment, which contributes to drug resistance via secretion of sEVs from senescent stromal cells. SIGNIFICANCE: Senescent stromal cells produce a large number of sEVs to promote cancer resistance in therapeutic settings, a process driven by SIRT1 decline in stromal cells and ABCB4 augmentation in cancer cells.

Indexed as

Extracellular VesiclesNeoplasmsCell Line, TumorCellular SenescenceHumansSirtuin 1Stromal CellsSIRT1 protein, humanSirtuin 1

Identifiers

PMID32366480
PMCPMC7611217
OpenAlexW3022305272

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.