Evidence map›Paper›PMID 33009373›Full record

ArticleCell death & disease2020

AFP promotes HCC progression by suppressing the HuR-mediated Fas/FADD apoptotic pathway.

Tianke Chen, Xiaowei Dai, Juji Dai, Chaodong Ding, Zheng Zhang, Ziqi Lin, Jin Hu, Mei Lu, Zhanyu Wang, Yalei Qi and 6 more

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

Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed, 1 pooled it
10.4field-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

100 citing papers in PubMed, 1 synthesis or guideline pooled it, 181 citations in OpenAlex.

  1. Pooled it
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  18. Hepatocellular Carcinoma: A Comprehensive Review.Diseases (Basel, Switzerland) · 2025
    Review
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40 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

16 authors at 1 institution in 1 country.

Tianke Chen *School of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, China.
Xiaowei Dai *School of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, China.
Juji Dai *School of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, China.
Chaodong Ding *School of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, China.
Zheng ZhangSchool of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, China.
Ziqi LinSchool of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, China.
Jin HuSchool of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, China.
Mei LuSchool of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, China.
Zhanyu WangSchool of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, China.
Yalei QiSchool of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, China.
Li ZhangSchool of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, China.
Rulu PanSchool of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, China.
Zhu ZhaoSchool of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, China.
Liting LuSchool of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, China.
Wanqin LiaoSchool of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, China.
Xincheng LuSchool of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, China. xinchenglu@yahoo.com.ORCID http://orcid.org/0000-0003-0858-7590
Wenzhou Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) is a major leading cause of cancer-related death worldwide. Alpha fetoprotein (AFP) is reactivated in a majority of hepatocellular carcinoma (HCC) and associated with poor patient outcomes. Although increasing evidence has shown that AFP can regulate HCC cell growth, the precise functions of AFP in hepatocarcinogenesis and the associated underlying mechanism remain incompletely understood. In this study, we demostrated that depleting AFP significantly suppressed diethylnitrosamine (DEN)-induced liver tumor progression in an AFP gene-deficient mouse model. Similarly, knocking down AFP expression inhibited human HCC cell proliferation and tumor growth by inducing apoptosis. AFP expression level was inversely associated with the apoptotic rate in mouse and human HCC specimens. Investigation of potential cross-talk between AFP and apoptotic signaling revealed that AFP exerted its growth-promoting effect by suppressing the Fas/FADD-mediated extrinsic apoptotic pathway. Mechanistically, AFP bound to the RNA-binding protein HuR, increasing the accumulation of HuR in the cytoplasm and subsequent inhibition of Fas mRNA translation. In addition, we found that inhibiting AFP enhanced the cytotoxicity of therapeutics to AFP-positive HCC cells by activating HuR-mediated Fas/FADD apoptotic signaling. Conclusion: Our study defined the pro-oncogenic role of AFP in HCC progression and uncovered a novel antiapoptotic mechanism connecting AFP to HuR-mediated Fas translation. Our findings suggest that AFP is involved in the pathogenesis and chemosensitivity of HCC and that blockade of AFP may be a promising strategy to treat advanced HCC.

Indexed as

alpha-FetoproteinsAnimalsApoptosisCarcinogenesisCarcinoma, HepatocellularCell Line, TumorFas-Associated Death Domain ProteinGene Expression Regulation, NeoplasticHumansLiver NeoplasmsMiceAFP protein, humanalpha-FetoproteinsFADD protein, humanFas-Associated Death Domain Protein

Identifiers

PMID33009373
PMCPMC7532541
OpenAlexW3090043634

What OpenQuestion holds

Textmetadata
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.