Evidence map›Paper›PMID 33947961›Full record

ArticleOncogene2021

Loss of DLX3 tumor suppressive function promotes progression of SCC through EGFR-ERBB2 pathway.

Deepti Bajpai, Spencer Mehdizadeh, Akihiko Uchiyama, Yuta Inoue, Andrew Sawaya, Andrew Overmiller, Stephen R Brooks, Kowser Hasneen, Meghan Kellett, Elisabetta Palazzo and 4 more

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

Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

4 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
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 3 institutions in 2 countries.

Deepti BajpaiLaboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, USA.
Spencer MehdizadehLaboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, USA.
Akihiko UchiyamaDepartment of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Yuta InoueDepartment of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Andrew SawayaLaboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, USA.
Andrew OvermillerLaboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, USA.
Stephen R BrooksBiodata Mining and Discovery Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, USA.
Kowser HasneenLaboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, USA.
Meghan KellettLaboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, USA.
Elisabetta PalazzoLaboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, USA.
Sei-Ichiro MotegiDepartment of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Stuart H YuspaLaboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
Christophe CataissonLaboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
Maria I MorassoLaboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, USA. morassom@mail.nih.gov.ORCID http://orcid.org/0000-0002-9632-9593
National Institute of Arthritis and Musculoskeletal and Skin Diseases · USGunma University · JPNational Cancer Institute · US

Funding

Regulation Of Epidermal DifferentiationZIAAR041124 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI MORASSO, MARIA · 2009 to 2024
$21.1M
Interacting Signaling Pathways that Initiate Squamous Cell CarcinogenesisZIABC004504 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI YUSPA, STUART H. · 2009 to 2022
$15.7M
Applying Bioinformatics to Research in Immune, Muscle, and Bone DiseasesZICAR041173 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI SUN, HONG-WEI · 2021 to 2025
$10.3M
REGULATION OF EPIDERMAL DIFFERENTIATIONZ01AR041124 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI MORASSO, MARIA I · 2000 to 2008
$1.9M
Intramural NIH HHS Z01 AR041124Intramural NIH HHS ZIA AR041124
6 · The paper itself

Abstract

Cutaneous squamous cell carcinoma (cSCC) ranks second in the frequency of all skin cancers. The balance between keratinocyte proliferation and differentiation is disrupted in the pathological development of cSCC. DLX3 is a homeobox transcription factor which plays pivotal roles in embryonic development and epidermal homeostasis. To investigate the impact of DLX3 expression on cSCC prognosis, we carried out clinicopathologic analysis of DLX3 expression which showed statistical correlation between tumors of higher pathologic grade and levels of DLX3 protein expression. Further, Kaplan-Meier survival curve analysis demonstrated that low DLX3 expression correlated with poor patient survival. To model the function of Dlx3 in skin tumorigenesis, a two-stage dimethylbenzanthracene (DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA) study was performed on mice genetically depleted of Dlx3 in skin epithelium (Dlx3cKO). Dlx3cKO mice developed significantly more tumors, with more rapid tumorigenesis compared to control mice. In Dlx3cKO mice treated only with DMBA, tumors developed after ~16 weeks suggesting that loss of Dlx3 has a tumor promoting effect. Whole transcriptome analysis of tumor and skin tissue from our mouse model revealed spontaneous activation of the EGFR-ERBB2 pathway in the absence of Dlx3. Together, our findings from human and mouse model system support a tumor suppressive function for DLX3 in skin and underscore the efficacy of therapeutic approaches that target EGFR-ERBB2 pathway.

Indexed as

9,10-Dimethyl-1,2-benzanthraceneAgedAnimalsCarcinogensCarcinoma, Squamous CellDisease Models, AnimalErb-b2 Receptor Tyrosine KinasesErbB ReceptorsFemaleHomeodomain ProteinsHumansMaleMiceMice, Inbred C57BLMice, KnockoutNeoplasm Grading9,10-Dimethyl-1,2-benzanthraceneCarcinogensDistal-less homeobox proteinsEGFR protein, humanERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesErbB ReceptorsHomeodomain ProteinsTetradecanoylphorbol AcetateTranscription Factors

Identifiers

PMID33947961
PMCPMC8159909
OpenAlexW3159968794

What OpenQuestion holds

Textmetadata
LicenceTDM
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.