TY - JOUR
T1 - Repression of bone morphogenetic protein 4 by let-7i attenuates mesenchymal migration of head and neck cancer cells
AU - Yang, Wen Hao
AU - Lan, Hsin Yi
AU - Tai, Shyh Kuan
AU - Yang, Muh Hwa
N1 - Funding Information:
This work was supported by National Health Research Institutes ( NHRI-EX100-10037BI to M.H.Y.), National Science Council ( 101-2321-B-010-007 to M.H.Y.), Taipei Veterans General Hospital ( V102-E8-002 ; V102C-036 to M.H.Y.), a grant from Ministry of Education , Aim for the Top University Plan (to M.H.Y.), and a grant from Department of Health, Center of Excellence for Cancer Research ( DOH101-TD-C-111-007 to M.H.Y).
PY - 2013/3/29
Y1 - 2013/3/29
N2 - The movement modes of epithelial cancer cells in three-dimensional (3D) environments include the mesenchymal mode, which is associated with local invasion, and the amoeboid mode, which facilitates distant metastasis. The migratory behavior of individual cancer cells is critical for tumor dissemination; however, the mechanism underlying regulation of the switch between movement modes is not clearly understood. For head and neck squamous cell carcinoma (HNSCC), local invasion is the major route of dissemination. We previously demonstrated that, in HNSCC cells, Twist1 represses let-7i expression to elicit mesenchymal-mode movement through activation of Ras-related C3 botulinum toxin substrate 1 (RAC1). In this study, we discover another important target gene of let-7i for regulating HNSCC migration. Using bioinformatic tools, we identified bone morphogenetic protein 4 (BMP4) as a candidate target of let-7i. Further experiments, including 3'-untranslated region (UTR) reporter assays, quantitative RT-PCR and western blotting, confirmed that BMP4 is a bona fide target repressed by let-7i. In the HNSCC cell line OECM-1, knockdown of BMP4 reduced mesenchymal-mode migration and invasion in 3D culture. In clinical HNSCC samples, let-7i expression was inversely correlated with BMP4 expression. Our results revealed that let-7i attenuates mesenchymal-mode migration of HNSCC cells through repression of a novel target, BMP4.
AB - The movement modes of epithelial cancer cells in three-dimensional (3D) environments include the mesenchymal mode, which is associated with local invasion, and the amoeboid mode, which facilitates distant metastasis. The migratory behavior of individual cancer cells is critical for tumor dissemination; however, the mechanism underlying regulation of the switch between movement modes is not clearly understood. For head and neck squamous cell carcinoma (HNSCC), local invasion is the major route of dissemination. We previously demonstrated that, in HNSCC cells, Twist1 represses let-7i expression to elicit mesenchymal-mode movement through activation of Ras-related C3 botulinum toxin substrate 1 (RAC1). In this study, we discover another important target gene of let-7i for regulating HNSCC migration. Using bioinformatic tools, we identified bone morphogenetic protein 4 (BMP4) as a candidate target of let-7i. Further experiments, including 3'-untranslated region (UTR) reporter assays, quantitative RT-PCR and western blotting, confirmed that BMP4 is a bona fide target repressed by let-7i. In the HNSCC cell line OECM-1, knockdown of BMP4 reduced mesenchymal-mode migration and invasion in 3D culture. In clinical HNSCC samples, let-7i expression was inversely correlated with BMP4 expression. Our results revealed that let-7i attenuates mesenchymal-mode migration of HNSCC cells through repression of a novel target, BMP4.
KW - BMP4
KW - Let-7i
KW - Mesenchymal migration
UR - http://www.scopus.com/inward/record.url?scp=84875813637&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2013.02.076
DO - 10.1016/j.bbrc.2013.02.076
M3 - Article
C2 - 23454123
AN - SCOPUS:84875813637
SN - 0006-291X
VL - 433
SP - 24
EP - 30
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
