Evidence map›Paper›PMID 31911278›Full record

ArticleTranslational oncology2020

VCAM-1 Upregulation Contributes to Insensitivity of Vemurafenib in BRAF-Mutant Thyroid Cancer.

Shitu Chen, Xingyun Su, Xiaoxia Jiang, Tuo Zhang, Irene Min, Yongfeng Ding, Xumeng Wang, Zhuochao Mao, Jiang Cao, Xiaodong Teng and 3 more

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

Article in Translational oncology, 2020. 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
1.3field-weighted citation impact, top 20% 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

13 citing papers in PubMed, 18 citations in OpenAlex.

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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 at 4 institutions in 2 countries.

Shitu ChenCancer Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Xingyun SuCancer Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Xiaoxia JiangCancer Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Tuo ZhangGenomic Core, Weill Cornell Medical College, New York, NY, USA.
Irene MinDepartment of Surgery, New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, NY, USA.
Yongfeng DingCancer Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Xumeng WangCancer Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Zhuochao MaoCancer Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Jiang CaoClinical Research Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Xiaodong TengDepartment of Pathology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Thomas J FaheyDepartment of Surgery, New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, NY, USA. Electronic address: tjfahey@med.cornell.edu.
Weibin WangCancer Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address: wbwang@zju.edu.cn.
Lisong TengCancer Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address: lsteng@zju.edu.cn.
Zhejiang University · CNPresbyterian Hospital · USCornell University · USSecond Affiliated Hospital of Zhejiang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Vemurafenib, an inhibitor of mutant BRAF activity, is a promising anticancer agent for patients with BRAF-mutant metastatic melanoma. However, it is less effective in BRAF-mutant thyroid cancer, and the reason for this discrepancy is not yet fully elucidated. By RNA sequencing analysis, we identified vascular cell adhesion molecular-1 (VCAM-1) to be highly upregulated in both time- and dose-dependent manners during BRAF inhibition (BRAFi) in a BRAF-mutant papillary thyroid cancer cell line (BCPAP). Cell cytotoxicity and apoptosis assays showed that knockdown of the induced VCAM-1 in BCPAP cells augmented the antitumor effects of vemurafenib, with decreased IC50 values of 1.4 to 0.8 μM. Meanwhile, overexpression of VCAM-1 in a BRAF-mutant anaplastic thyroid cancer cell line (FRO) reduced the sensitivity to vemurafenib, with increased IC50 values of 1.9 to 5.8 μM. Further investigation showed that PI3K-Akt-mTOR pathway was activated during BRAFi. Co-treatment with Akt signaling inhibitor MK2206 decreased the induced expression of VCAM-1 during BRAFi. This combination further improved the efficacy of vemurafenib. Moreover, VCAM-1 promoted migration and invasion in thyroid cancer cells in vitro, which was also indicated in thyroid cancer patients. The present study is the first to demonstrate that VCAM-1 is upregulated in thyroid cancer cells treated with vemurafenib and contributes to vemurafenib resistance in BRAF-mutant thyroid cancer cells. Targeting the PI3K-Akt-mTOR pathway-mediated VCAM-1 response may be an alternative strategy to sensitize BRAF-mutant thyroid cancers to vemurafenib.

Identifiers

PMID31911278
PMCPMC6948368
OpenAlexW2998516834

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.