β1 integrins mediate cell proliferation in three-dimensional cultures by regulating expression of the sonic hedgehog effector protein, GLI1
| Autor: | Jeffrey A. Nickerson, Chung-Cheng Hsieh, Jean M. Underwood, Lucia R. Languino, Hira Lal Goel |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Physiology Recombinant Fusion Proteins Clinical Biochemistry Integrin Cell Culture Techniques Integrin alpha5 Transfection Zinc Finger Protein GLI1 Article Receptor IGF Type 1 Downregulation and upregulation GLI1 Cell Line Tumor Humans Insulin-Like Growth Factor I Phosphorylation Sonic hedgehog Protein kinase B Cell Proliferation biology Cell growth Akt/PKB signaling pathway Integrin beta1 Prostatic Neoplasms Cell Biology biology.protein Cancer research Tyrosine RNA Interference Signal transduction Proto-Oncogene Proteins c-akt Signal Transduction Transcription Factors |
| Zdroj: | Journal of Cellular Physiology. |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.22116 |
| Popis: | The β1 integrins play an important role in the modulation of cancer cell proliferation and tumor growth. We have previously shown that β1 integrins associate with insulin-like growth factor type 1 receptor (IGF-IR) and regulate IGF-stimulated prostate cancer cell proliferation. In the present study, we find that downregulation of β1 in prostate cancer cells inhibits IGF-IR and AKT activation. We also show that β1 downregulation in prostate cancer two- and three-dimensional (3-D) cell cultures significantly reduces expression of GLI1, a transcription factor known to be regulated by the IGF/AKT signaling pathway and to be a downstream effector of sonic hedgehog. Re-expression of GLI1 rescues the inhibitory effect of β1 downregulation on prostate cancer cell proliferation in 3-D cultures. We find that downregulation of β1 reduces surface expression of associated α integrin subunits, predominantly α5 and at a lower extent: α2, α3 and α4. Our results indicate that the β1/IGF-IR complex regulates expression of GLI1, which in turn promotes cancer cell proliferation in 3-D cultures. |
| Databáze: | OpenAIRE |
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