Evidence map›Paper›PMID 32623326›Full record

ArticleTranslational oncology2020

Skp2 depletion reduces tumor-initiating properties and promotes apoptosis in synovial sarcoma.

Jichuan Wang, Kenji Sato, Ed O'Donnell, Amit Singla, Simon Yaguare, Osama Aldahamsheh, Brian Batko, Hasibagan Borjihan, Janet Tingling, Jinghang Zhang and 9 more

Open access · goldAbstract read
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 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.9field-weighted citation impact, top 11% 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

14 citing papers in PubMed, 20 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

19 authors at 5 institutions in 2 countries.

Jichuan WangDepartment of Orthopedic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Musculoskleletal Tumor Center, Beijing Key Laboratory for Musculoskeletal Tumors, Peking University People's Hospital, Beijing, China.
Kenji SatoDepartment of Orthopedic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Ed O'DonnellDepartment of Orthopedic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Amit SinglaDepartment of Orthopedic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Simon YaguareDepartment of Orthopedic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Osama AldahamshehDepartment of Orthopedic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Brian BatkoDepartment of Orthopedic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Hasibagan BorjihanDepartment of Orthopedic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Janet TinglingDepartment of Orthopedic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Jinghang ZhangFlow Cytometry Core Facility, Albert Einstein College of Medicine, Bronx, NY.
Daniel A WeiserDivision of Pediatric Hematology-Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY.
David M LoebDivision of Pediatric Hematology-Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY.
Richard GorlickDivision of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, TX.
Edward L SchwartzDepartments of Medicine (Oncology) and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY.
Rui YangDepartment of Orthopedic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Xiaolin ZiDepartment of Urology, University of California, Irvine Medical Center, Orange, CA.
Hongling ZhaoDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY.
David S GellerDepartment of Orthopedic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Bang H HoangDepartment of Orthopedic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY. Electronic address: bahoang@montefiore.org.
Albert Einstein College of Medicine · USMontefiore Medical Center · USChildren's Hospital at Montefiore · USThe University of Texas MD Anderson Cancer Center · USUniversity of California, Irvine Medical Center · US

Funding

Vulnerability of SCLC based on bi-allelic genetic inactivation of RB1 and TP53R01CA230032 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI SCHWARTZ, EDWARD L, ZHAO, HONGLING · 2019 to 2024
$2.0M
The NEDD8 pathway mediated Skp2 degradation in chemoprevention by FKAR01CA193967 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI ZI, XIAOLIN · 2016 to 2020
$1.8M
NCI NIH HHS R01 CA193967NCI NIH HHS R01 CA230032
6 · The paper itself

Abstract

Synovial sarcoma (SS) is an aggressive soft-tissue cancer with a poor prognosis and a propensity for local recurrence and distant metastasis. In this study, we investigated whether S phase kinase-associated protein (Skp2) plays an oncogenic role in tumor initiation, progression, and metastasis of SS. Our study revealed that Skp2 is frequently overexpressed in SS specimens and SS18-SSX transgenic mouse tumors, as well as correlated with clinical stages. Next, we identified that genetic depletion of Skp2 reduced mesenchymal and stemness markers, and inhibited the invasive and proliferative capacities of SS cell lines. Furthermore, Skp2 depletion markedly suppressed the growth of SS xenografts tumors. Treatment of SS cell lines with the skp2 inhibitor flavokawain A (FKA) reduced Skp2 expression in a dose-dependent manner and resulted in cell cycle arrest and apoptosis. FKA also suppressed the invasion and tumor-initiating properties in SS, similar to the effects of Skp2 knockdown. In addition, a combination of FKA and conventional chemotherapy showed a synergistic therapeutic efficacy. Taken together, our results suggest that Skp2 plays an essential role in the biology of SS by promoting the mesenchymal state and cancer stemness. Given that chemotherapy resistance is often associated with cancer stemness, strategies of combining Skp2 inhibitors with conventional chemotherapy in SS may be desirable.

Identifiers

PMID32623326
PMCPMC7334610
OpenAlexW3039927900

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.