Evidence map›Paper›PMID 31064356›Full record

ArticleMolecular cancer2019

CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer.

J L Hu, W Wang, X L Lan, Z C Zeng, Y S Liang, Y R Yan, F Y Song, F F Wang, X H Zhu, W J Liao and 3 more

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 502 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
502citing papers in PubMed, 2 pooled it
34.9field-weighted citation impact, top 1% 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

502 citing papers in PubMed, 2 syntheses or guidelines pooled it, 796 citations in OpenAlex.

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442 more citing papers are in PubMed but not listed here.

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 at 2 institutions in 1 country.

J L HuDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China.
W WangDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China.
X L LanDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China.
Z C ZengDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China.
Y S LiangDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China.
Y R YanDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China.
F Y SongDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China.
F F WangDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China.
X H ZhuDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China.
W J LiaoDepartment of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong province, People's Republic of China.
W T LiaoDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China.
Y Q DingDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China.
L LiangDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China. redsnow007@hotmail.com.
Southern Medical University · CNNanfang Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) metastasis and chemoresistance have not been fully characterized.

methodsCAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1.

resultsCAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/β-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients.

conclusionsCAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.

Indexed as

Drug Resistance, NeoplasmAdaptor Proteins, Signal TransducingAnimalsApoptosis Regulatory ProteinsCancer-Associated FibroblastsCell Line, TumorColorectal NeoplasmsEpithelial-Mesenchymal TransitionExosomesF-Box-WD Repeat-Containing Protein 7Gene Expression Regulation, NeoplasticHumansLiver NeoplasmsMiceMicroRNAsNeoplasm TransplantationAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsF-Box-WD Repeat-Containing Protein 7FBXW7 protein, humanMicroRNAsMIRN92 microRNA, humanMOAP1 protein, humanChemotherapy resistanceColorectal cancerExosomesMetastasismiR-92a-3pStemness

Identifiers

PMID31064356
PMCPMC6503554
OpenAlexW2947891482

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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.