RGD Reference Report - SOX4, an epithelial-mesenchymal transition inducer, transactivates ADAM28 gene expression and co-localizes with ADAM28 at the invasive front of human breast and lung carcinomas. - Rat Genome Database

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SOX4, an epithelial-mesenchymal transition inducer, transactivates ADAM28 gene expression and co-localizes with ADAM28 at the invasive front of human breast and lung carcinomas.

Authors: Sasaki, Aya  Abe, Hitoshi  Mochizuki, Satsuki  Shimoda, Masayuki  Okada, Yasunori 
Citation: Sasaki A, etal., Pathol Int. 2018 Jun 7. doi: 10.1111/pin.12685.
RGD ID: 153297792
Pubmed: PMID:29882245   (View Abstract at PubMed)
DOI: DOI:10.1111/pin.12685   (Journal Full-text)

ADAM28 (a disintegrin and metalloproteinase 28) is abundantly expressed by carcinoma cells in the human breast and non-small cell lung carcinomas, and plays a role in carcinoma cell growth and metastasis. Although Src is an inducer of ADAM28 gene expression through the PI3K/AKT/mTOR and MEK/ERK pathways, direct transcriptional regulators for ADAM28 gene expression remain unknown. In this study, we performed the luciferase reporter assay and found that SOX4 (SRY-related HMG-box 4), an inducer of epithelial-mesenchymal transition (EMT), is a transcriptional activator for the ADAM28 gene. This activation required the SOX4-binding consensus sequence at the 5'-untranslated region of the mouse and human ADAM28 genes. Forced expression of SOX4 promoted the ADAM28 gene expression and migration in human breast and lung carcinoma cell lines. In the human breast and lung carcinoma tissues, ADAM28 and SOX4 were co-expressed at the invasive front of carcinoma cell nests. Our data demonstrate that SOX4 transactivates ADAM28 gene expression through direct binding to the ADAM28 promoter region and suggest the possibility that ADAM28 plays a role in invasion through SOX4-mediated EMT in the human breast and lung carcinomas.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
breast carcinoma  IEP 153297792; 153297792protein:increased expression:breastRGD 
breast carcinoma  ISOADAM28 (Homo sapiens)153297792; 153297792protein:increased expression:breastRGD 
breast carcinoma  ISOSOX4 (Homo sapiens)153297792; 153297792protein:increased expression:breastRGD 
lung adenocarcinoma  IEP 153297792; 153297792protein:increased expression:lungRGD 
lung adenocarcinoma  ISOADAM28 (Homo sapiens)153297792; 153297792protein:increased expression:lungRGD 
lung adenocarcinoma  ISOSOX4 (Homo sapiens)153297792; 153297792protein:increased expression:lungRGD 

Objects Annotated

Genes (Rattus norvegicus)
Adam28  (ADAM metallopeptidase domain 28)
Sox4  (SRY-box transcription factor 4)

Genes (Mus musculus)
Adam28  (a disintegrin and metallopeptidase domain 28)
Sox4  (SRY (sex determining region Y)-box 4)

Genes (Homo sapiens)
ADAM28  (ADAM metallopeptidase domain 28)
SOX4  (SRY-box transcription factor 4)


Additional Information