ZIC1 overexpression is oncogenic in liposarcoma Journal Article
| Authors: | Brill, E.; Gobble, R.; Angeles, C.; Lagos-Quintana, M.; Crago, A.; Laxa, B.; Decarolis, P.; Zhang, L.; Antonescu, C.; Socci, N. D.; Taylor, B. S.; Sander, C.; Koff, A.; Singer, S. |
| Article Title: | ZIC1 overexpression is oncogenic in liposarcoma |
| Abstract: | Liposarcomas are aggressive mesenchymal cancers with poor outcomes that exhibit remarkable histologic diversity (there are five recognized subtypes). Currently, the mainstay of therapy for liposarcoma is surgical excision because liposarcomas are often resistant to traditional chemotherapy. In light of the high mortality associated with liposarcoma and the lack of effective systemic therapy, we sought novel genomic alterations driving liposarcomagenesis that might serve as therapeutic targets. ZIC1, a critical transcription factor for neuronal development, is overexpressed in all five subtypes of liposarcoma compared with normal fat, and in liposarcoma cell lines compared with adipose-derived stem cells. Here, we show that ZIC1 contributes to the pathogenesis of liposarcoma. ZIC1 knockdown inhibits proliferation, reduces invasion, and induces apoptosis in dedifferentiated and myxoid/round cell liposarcoma cell lines, but not in either adipose-derived stem cells or in a lung cancer cell line with low ZIC1 expression. ZIC1 knockdown is associated with increased nuclear expression of p27 proteins and the downregulation of prosurvival target genes BCL2L13, JunD, Fam57A, and EIF3M. Our results show that ZIC1 expression is essential for liposarcomagenesis and that targeting ZIC1 or its downstream targets might lead to novel therapy for liposarcoma. ©2010 AACR. |
| Keywords: | controlled study; human tissue; protein expression; human cell; major clinical study; dna replication; cell proliferation; gene overexpression; apoptosis; gene expression profiling; rna, small interfering; gene function; cell differentiation; cancer cell culture; cell line, tumor; carcinogenesis; transcription factors; stem cell; gene expression regulation; oncogene; reverse transcriptase polymerase chain reaction; protein p27; cell growth processes; cyclin-dependent kinase inhibitor p27; down regulation; neoplasm invasiveness; cell invasion; short hairpin rna; gene knockdown techniques; liposarcoma; myxosarcoma; small cell sarcoma; cell dedifferentiation; sarcoma cell; zic1 gene |
| Journal Title: | Cancer Research |
| Volume: | 70 |
| Issue: | 17 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2010-09-01 |
| Start Page: | 6891 |
| End Page: | 6901 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-10-0745 |
| PUBMED: | 20713527 |
| PROVIDER: | scopus |
| PMCID: | PMC3266950 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: CNREA" - "Source: Scopus" |
