Evidence map›Paper›PMID 32024555›Full record

ArticleJournal of hematology & oncology2020

CD73 sustained cancer-stem-cell traits by promoting SOX9 expression and stability in hepatocellular carcinoma.

Xiao-Lu Ma, Bo Hu, Wei-Guo Tang, Su-Hong Xie, Ning Ren, Lin Guo, Ren-Quan Lu

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hematology & oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed
12.3field-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

98 citing papers in PubMed, 151 citations in OpenAlex.

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38 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

7 authors at 4 institutions in 1 country.

Xiao-Lu MaDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical School, Fudan University, Shanghai, 200032, China.
Bo HuDepartment of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Wei-Guo TangDepartment of Hepatobiliary and Pancreatic Surgery, Minhang Hospital, Fudan University, Shanghai, 201100, China.
Su-Hong XieDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical School, Fudan University, Shanghai, 200032, China.
Ning RenDepartment of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. ren.ning@zs-hospital.sh.cn.
Lin GuoDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical School, Fudan University, Shanghai, 200032, China. Guolin500@hotmail.com.
Ren-Quan LuDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical School, Fudan University, Shanghai, 200032, China. dadagis10@163.com.
Fudan University · CNFudan University Shanghai Cancer Center · CNShanghai Medical College of Fudan University · CNMinhang District Central Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAberrant AKT activation contributes to cancer stem cell (CSC) traits in hepatocellular carcinoma (HCC). We previously reported that CD73 activated AKT signaling via the Rap1/P110β cascade. Here, we further explored the roles of CD73 in regulating CSC characteristics of HCC.

methodsCD73 expression modulations were conducted by lentiviral transfections. CD73+ fractions were purified by magnetic-based sorting, and fluorescent-activated cell sorting was used to assess differentiation potentials. A sphere-forming assay was performed to evaluate CSC traits in vitro, subcutaneous NOD/SCID mice models were generated to assess in vivo CSC features, and colony formation assays assessed drug resistance capacities. Stemness-associated gene expression was also determined, and underlying mechanisms were investigated by evaluating immunoprecipitation and ubiquitylation.

resultsWe found CD73 expression was positively associated with sphere-forming capacity and elevated in HCC spheroids. CD73 knockdown hindered sphere formation, Lenvatinib resistance, and stemness-associated gene expression, while CD73 overexpression achieved the opposite effects. Moreover, CD73 knockdown significantly inhibited the in vivo tumor propagation capacity. Notably, we found that CD73+ cells exhibited substantially stronger CSC traits than their CD73- counterparts. Mechanistically, CD73 exerted its pro-stemness activity through dual AKT-dependent mechanisms: activating SOX9 transcription via c-Myc, and preventing SOX9 degradation by inhibiting glycogen synthase kinase 3β. Clinically, the combined analysis of CD73 and SOX9 achieved a more accurate prediction of prognosis.

conclusionsCollectively, CD73 plays a critical role in sustaining CSCs traits by upregulating SOX9 expression and enhancing its protein stability. Targeting CD73 might be a promising strategy to eradicate CSCs and reverse Lenvatinib resistance in HCC.

Indexed as

Gene Expression Regulation, Neoplastic5'-NucleotidaseCarcinoma, HepatocellularCell Line, TumorGPI-Linked ProteinsHumansLiver NeoplasmsNeoplastic Stem CellsSOX9 Transcription Factor5'-NucleotidaseGPI-Linked ProteinsNT5E protein, humanSOX9 protein, humanSOX9 Transcription FactorAKT signalingCancer stem cellsCD73Hepatocellular carcinomaLenvatinib resistance

Identifiers

PMID32024555
PMCPMC7003355
OpenAlexW3005526718

What OpenQuestion holds

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LicenceCC BY
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.