Abstract | BACKGROUND:
Metastasis is most often the root cause of cancer-related death. Human short stature homeobox 2 (SHOX2), a homeodomain transcription factor, is a novel inducer of epithelial-to-mesenchymal transition in breast cancer cells, though its exact role and underlying mechanisms in metastasis are not well understood. METHODS: TCGA analysis was performed to identify the clinical relevance of SHOX2 in breast cancer. Gene depletion was achieved by short hairpin RNA and small interfering RNA. Molecular regulations and alterations were assessed by Western blotting, immunoprecipitation, immunohistochemistry, qRT-PCR, chromatin immunoprecipitation coupled with qPCR (ChIP-qPCR), and ChIP/re-ChIP. The impact of SHOX2 signaling on tumor growth and metastasis was evaluated in orthotopic breast tumor mice. RESULTS: CONCLUSIONS: These findings provide a critical link between the SHOX2-STAT3-WASF3 signaling axis and metastasis and suggest that the targeting of this signaling node may represent a valuable alternative strategy for combating breast cancer metastasis.
|
Authors | Yong Teng, Reid Loveless, Elayne M Benson, Li Sun, Austin Y Shull, Chloe Shay |
Journal | Journal of experimental & clinical cancer research : CR
(J Exp Clin Cancer Res)
Vol. 40
Issue 1
Pg. 274
(Aug 31 2021)
ISSN: 1756-9966 [Electronic] England |
PMID | 34465361
(Publication Type: Journal Article)
|
Copyright | © 2021. The Author(s). |
Chemical References |
- Homeodomain Proteins
- SHOX2 protein, human
- STAT3 Transcription Factor
- STAT3 protein, human
- WASF3 protein, human
- Wiskott-Aldrich Syndrome Protein Family
|
Topics |
- Animals
- Breast Neoplasms
(pathology)
- Cell Line, Tumor
- Cell Proliferation
- Female
- Homeodomain Proteins
(metabolism)
- Humans
- Mice
- Mice, Inbred NOD
- Neoplasm Metastasis
- Promoter Regions, Genetic
- Protein Binding
- STAT3 Transcription Factor
(metabolism)
- Signal Transduction
- Transcriptional Activation
- Wiskott-Aldrich Syndrome Protein Family
(genetics)
|