CORRIGENDUM: Stage of Breast Cancer Progression Influences Cellular Response to Activation of the WNT/Planar Cell Polarity Pathway
| Autor: | Ann F. Chambers, Hon S. Leong, Amy E. Robertson, Connor D. MacMillan, John D. Lewis, Alan B. Tuck, David W. Dales |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
RHOA
Context (language use) Breast Neoplasms Wnt-5a Protein Cell Movement Cell Line Tumor Proto-Oncogene Proteins Humans Neoplasm Invasiveness RNA Messenger RNA Small Interfering Wnt Signaling Pathway Gene knockdown Multidisciplinary biology Chemistry Wnt signaling pathway Cell Polarity Membrane Proteins Ductal carcinoma Corrigenda Extravasation body regions WNT5A Transcription Factor AP-1 Wnt Proteins Cell culture Cyclooxygenase 2 embryonic structures biology.protein Cancer research Disease Progression Female Matrix Metalloproteinase 3 RNA Interference sense organs Carrier Proteins rhoA GTP-Binding Protein |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Planar cell polarity (PCP) signaling has been shown in different studies to either promote or inhibit the malignancy of breast cancer. Using the 21T cell lines, which were derived from an individual patient and represent distinct stages of progression, we show that the prototypical PCP ligand, WNT5A, is expressed highest in 21MT-1 cells (invasive mammary carcinoma) and lowest in 21PT (atypical ductal hyperplasia) and 21NT (ductal carcinoma in situ) cells. Overexpression of WNT5A decreased spherical colony formation and increased invasion and in vivo extravasation only in 21NT cells; whereas overexpression increased migration of both 21PT and 21NT cells. WNT5A overexpression also increased RHOA expression of both cell lines and subsequent RHOA knockdown blocked WNT5A-induced migration, but only partially blocked WNT5A-induced invasion of 21NT cells. PCP can signal through VANGL1 to modulate AP-1 target genes (e.g. MMP3) and induce invasion. VANGL1 knockdown inhibited WNT5A-induced invasion of 21NT cells, but had no effect on WNT5A-induced migration of either 21PT or 21NT cells. WNT5A-induced MMP3 expression was seen only in 21NT cells, an effect that was VANGL1 dependent, but independent of AP-1. We thus provide evidence that PCP signaling can act in a context dependent manner to promote breast cancer progression. |
| Databáze: | OpenAIRE |
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