In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 4142-4142
Abstract:
Oral squamous cell carcinomas (OSCC) have a poor patient prognosis, which is attributed to their invasive nature. Our goal was to identify a novel gene that is important in OSCC invasion. We utilized genome-wide expression data generated from OSCC patient tumor samples with varying degrees of invasiveness, as measured by the histological parameter worst pattern of invasion (WPOI). RNA extracted from tumors that were classified as either WPOI 5 or WPOI 3, two categories of tumors that have been previously shown to correlate with local recurrence and poor overall survival, were evaluated utilizing two microarray platforms. When both gene expression datasets were analyzed, we identified 104 genes that were overexpressed at least 1.5-fold in the WPOI type 5 tumors compared to the less invasive WPOI type 3 tumors. Fifty genes were chosen based on functional criteria to be assessed using in vitro invasion assays following treatment with siRNA pools. In our initial screen, 16 of these genes showed significant reductions in in vitro invasion when their expression was knocked down by siRNA treatment in the UMSCC1 cell line. The gene with the greatest effect on invasion from the screen was Apolipoprotein E (APOE). In addition to in vitro invasion, we also observed that matrix degradation and mature invadopodia numbers were decreased with APOE knockdown in the UMSCC1 cell line, suggesting that APOE affects invasion in part through regulating invadopodial activity. We observed that APOE knockdown resulted in decreased phospho-cJun and phospho-ERK1/2 in the UMSCC1 and PCI-15B cell lines. Since cJun is a component of the AP1 transcription factor, we assessed AP1 promoter activity using a luciferase reporter assay. We found that AP1 promoter activity decreased with APOE knockdown in both cell lines. Our proposed model is that APOE knockdown suppresses the cells’ ability to invade via decreased activation of ERK1/2 and cJun, thus reducing AP1 transcriptional activity. Further studies are being done to determine which downstream targets of AP1 are being altered with APOE knockdown and if those targets are known to be implicated in invasion. Citation Format: Sangeeta K. Jayakar, Olivier D. Loudig, Margaret Brandwein-Gensler, Ryung Kim, Thomas J. Ow, Michael B. Prystowsky, Geoffrey Childs, Jeffrey E. Segall, Thomas J. Belbin. A role for apolipoprotein E in invasion in oral squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4142. doi:10.1158/1538-7445.AM2015-4142
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2015-4142
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
