Evidence map›Paper›PMID 27001612›Full record

ArticleGynecologic oncology2016

The High Mobility Group A1 (HMGA1) gene is highly overexpressed in human uterine serous carcinomas and carcinosarcomas and drives Matrix Metalloproteinase-2 (MMP-2) in a subset of tumors.

Joelle Hillion, Sujayita Roy, Mohammad Heydarian, Leslie Cope, Lingling Xian, Michael Koo, Li Z Luo, Kathleen Kellyn, Brigitte M Ronnett, Tait Huso and 4 more

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

Article in Gynecologic oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.8field-weighted citation impact, top 17% 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

23 citing papers in PubMed, 31 citations in OpenAlex.

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  15. Clinical Implications of Extracellular HMGA1 in Breast Cancer.International journal of molecular sciences · 2019
    Review
  16. Article
  17. Overexpression ofGenes · 2019
    Article
  18. HMGA1 in cancer: Cancer classification by location.Journal of cellular and molecular medicine · 2019
    Review
  19. Article
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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

14 authors at 2 institutions in 1 country.

Joelle HillionHematology Division, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Sujayita RoyHematology Division, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Mohammad HeydarianDepartment of Biologic Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Leslie CopeDepartment of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Lingling XianHematology Division, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Michael KooHematology Division, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Li Z LuoHematology Division, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Kathleen KellynPathobiology Graduate Program, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Brigitte M RonnettPathobiology Graduate Program, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Tait HusoHematology Division, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Deborah ArmstrongDepartment of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Karen ReddyDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Biologic Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
David L HusoDepartment of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
L M S ResarHematology Division, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Pathobiology Graduate Program, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Institute for Cellular Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States. Electronic address: lresar@jhmi.edu.
Johns Hopkins Medicine · USJohns Hopkins University · US

Funding

Zebrafish CoreP01CA134292 · NCI · JOHNS HOPKINS UNIVERSITY · PI LEACH, STEVEN D · 2009 to 2013
$7.4M
Mechanisms of Neoplastic Transformation by HMG-I/YR01CA092339 · NCI · JOHNS HOPKINS UNIVERSITY · PI RESAR, LINDA M S · 2003 to 2006
$1.2M
HMGA1 in Tumor Progression in Breast CancerR21CA149550 · NCI · JOHNS HOPKINS UNIVERSITY · PI RESAR, LINDA M S · 2010 to 2011
$387k
The Role of HMG-I/Y in Uterine CancerR21CA118343 · NCI · JOHNS HOPKINS UNIVERSITY · PI RESAR, LINDA M S · 2006 to 2007
$337k
Targeting HMGA1 in Pancreatic Tumor ProgressionR03CA139331 · NCI · JOHNS HOPKINS UNIVERSITY · PI RESAR, LINDA M S · 2009 to 2010
$164k
NCI NIH HHS P01 CA134292NCI NIH HHS R01 CA092339NCI NIH HHS R03 CA139331NCI NIH HHS R21 CA118343NCI NIH HHS R21 CA149550
6 · The paper itself

Abstract

objectivesAlthough uterine cancer is the fourth most common cause for cancer death in women worldwide, the molecular underpinnings of tumor progression remain poorly understood. The High Mobility Group A1 (HMGA1) gene is overexpressed in aggressive cancers and high levels portend adverse outcomes in diverse tumors. We previously reported that Hmga1a transgenic mice develop uterine tumors with complete penetrance. Because HMGA1 drives tumor progression by inducing MatrixMetalloproteinase (MMP) and other genes involved in invasion, we explored the HMGA1-MMP-2 pathway in uterine cancer.

methodsTo investigate MMP-2 in uterine tumors driven by HMGA1, we used a genetic approach with mouse models. Next, we assessed HMGA1 and MMP-2 expression in primary human uterine tumors, including low-grade carcinomas (endometrial endometrioid) and more aggressive tumors (endometrial serous carcinomas, uterine carcinosarcomas/malignant mesodermal mixed tumors).

resultsHere, we report for the first time that uterine tumor growth is impaired in Hmga1a transgenic mice crossed on to an Mmp-2 deficient background. In human tumors, we discovered that HMGA1 is highest in aggressive carcinosarcomas and serous carcinomas, with lower levels in the more indolent endometrioid carcinomas. Moreover, HMGA1 and MMP-2 were positively correlated, but only in a subset of carcinosarcomas. HMGA1 also occupies the MMP-2 promoter in human carcinosarcoma cells.

conclusionsTogether, our studies define a novel HMGA1-MMP-2 pathway involved in a subset of human carcinosarcomas and tumor progression in murine models. Our work also suggests that targeting HMGA1 could be effective adjuvant therapy for more aggressive uterine cancers and provides compelling data for further preclinical studies.

Indexed as

AnimalsCarcinosarcomaChromatin ImmunoprecipitationCystadenocarcinoma, SerousFemaleGene SilencingHMGA1a ProteinHumansMaleMatrix Metalloproteinase 2Mice, TransgenicPromoter Regions, GeneticUp-RegulationUterine NeoplasmsHMGA1a ProteinMatrix Metalloproteinase 2MMP2 protein, humanChromatin remodeling proteinsHigh Mobility Group A1HMGA1MMP-2Tumor progressionUterine cancer

Identifiers

PMID27001612
PMCPMC5770984
OpenAlexW2323707553

What OpenQuestion holds

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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.