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Conference Paper: Id1/IGF2/IGF1R/PI3K/AKT signaling cascade as functional markers and therapeutic targets in esophageal cancer

TitleId1/IGF2/IGF1R/PI3K/AKT signaling cascade as functional markers and therapeutic targets in esophageal cancer
Authors
KeywordsMedical sciences
Oncology
Issue Date2013
PublisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/ejca
Citation
The 2013 Joint Meeting by ASCO, EORTC and NCI, Brussels, Belgium, 7-9 November 2013. In European Journal of Cancer, 2013, v. 49 suppl. 4, p. S23, abstract no. MC13-0039 How to Cite?
AbstractBACKGROUND: Mounting evidence suggests that growth factors secreted by cancer cells play important roles in cancer progression. Id1 is commonly overexpressed in solid tumors including esophageal squamous cell carcinoma (ESCC). PURPOSE/OBJECTIVE: We aim to determine if the functions of Id1 in promoting cancer progression and chemoresistance are mediated by growth factors, investigate the autocrine/endocrine effects of the key Id1-induced growth factor, and evaluate the treatment efficiency of relevant anticancer therapeutic strategies. MATERIALS AND METHODS: Antibody array-based screening was used to identify differentially secreted growth factors from Id1-overexpressing ESCC cells. In vitro and in vivo assays were performed to confirm the induction of IGF2 by Id1, and to study the autocrine and endocrine effects of IGF2 in promoting ESCC progression. Human ESCC tissue microarray was analyzed for overexpression of IGF2 and its correlation with that of Id1 and p-AKT. Fluorouracil (5-FU)-resistant ESCC sublines were established by treating cells with increasing doses of 5-FU, and gene expression profiles were compared with the parental cells by cDNA microarray. The anti-tumor and anti-metastatic efficacies of IGF2 antibody and PI3K inhibitor wortmannin were evaluated using tumor xenograft and experimental metastasis models. RESULTS: Id1 overexpression induced IGF2 secretion which promoted cancer cell proliferation, survival and invasion by activating AKT in an autocrine manner. IGF2 secreted by Id1-overexpressing ESCC xenograft could instigate the growth of distant esophageal tumors, as well as promote metastasis of circulating cancer cells in an endocrine manner. Tissue microarray data showed overexpression of IGF2 in 21/35 (60%) human ESCC tissues which was associated with up-regulation of Id1 and p-AKT. Moreover, Id1 was identified by cDNA microarray analysis as being up-regulated in 5-FUresistant ESCC sublines; gain- and loss-of-function experiments confirmed its importance in increasing chemoresistance. We found that IGF2 antibody and wortmannin treatment significantly suppressed tumor growth, metastasis, and chemoresistance in mouse models. CONCLUSIONS: Our study demonstrated that the Id1/IGF2/PI3K/AKT signaling cascade plays an important role in esophageal cancer progression and chemoresistance. Blockade of IGF2/PI3K/AKT signaling has therapeutic potential in the management of esophageal cancer.
DescriptionThis journal suppl. entitled: Markers in Cancer: A joint meeting by ASCO, EORTC and NCI Abstract Book
Conference Theme: Markers in Cancer
Poster Presentation
Persistent Identifierhttp://hdl.handle.net/10722/193265
ISSN
2015 Impact Factor: 6.163
2015 SCImago Journal Rankings: 3.152

 

DC FieldValueLanguage
dc.contributor.authorLi, Ben_US
dc.contributor.authorTsao, Gen_US
dc.contributor.authorChan, Ken_US
dc.contributor.authorCheung, Aen_US
dc.date.accessioned2013-12-20T02:42:07Z-
dc.date.available2013-12-20T02:42:07Z-
dc.date.issued2013en_US
dc.identifier.citationThe 2013 Joint Meeting by ASCO, EORTC and NCI, Brussels, Belgium, 7-9 November 2013. In European Journal of Cancer, 2013, v. 49 suppl. 4, p. S23, abstract no. MC13-0039en_US
dc.identifier.issn0959-8049-
dc.identifier.urihttp://hdl.handle.net/10722/193265-
dc.descriptionThis journal suppl. entitled: Markers in Cancer: A joint meeting by ASCO, EORTC and NCI Abstract Book-
dc.descriptionConference Theme: Markers in Cancer-
dc.descriptionPoster Presentation-
dc.description.abstractBACKGROUND: Mounting evidence suggests that growth factors secreted by cancer cells play important roles in cancer progression. Id1 is commonly overexpressed in solid tumors including esophageal squamous cell carcinoma (ESCC). PURPOSE/OBJECTIVE: We aim to determine if the functions of Id1 in promoting cancer progression and chemoresistance are mediated by growth factors, investigate the autocrine/endocrine effects of the key Id1-induced growth factor, and evaluate the treatment efficiency of relevant anticancer therapeutic strategies. MATERIALS AND METHODS: Antibody array-based screening was used to identify differentially secreted growth factors from Id1-overexpressing ESCC cells. In vitro and in vivo assays were performed to confirm the induction of IGF2 by Id1, and to study the autocrine and endocrine effects of IGF2 in promoting ESCC progression. Human ESCC tissue microarray was analyzed for overexpression of IGF2 and its correlation with that of Id1 and p-AKT. Fluorouracil (5-FU)-resistant ESCC sublines were established by treating cells with increasing doses of 5-FU, and gene expression profiles were compared with the parental cells by cDNA microarray. The anti-tumor and anti-metastatic efficacies of IGF2 antibody and PI3K inhibitor wortmannin were evaluated using tumor xenograft and experimental metastasis models. RESULTS: Id1 overexpression induced IGF2 secretion which promoted cancer cell proliferation, survival and invasion by activating AKT in an autocrine manner. IGF2 secreted by Id1-overexpressing ESCC xenograft could instigate the growth of distant esophageal tumors, as well as promote metastasis of circulating cancer cells in an endocrine manner. Tissue microarray data showed overexpression of IGF2 in 21/35 (60%) human ESCC tissues which was associated with up-regulation of Id1 and p-AKT. Moreover, Id1 was identified by cDNA microarray analysis as being up-regulated in 5-FUresistant ESCC sublines; gain- and loss-of-function experiments confirmed its importance in increasing chemoresistance. We found that IGF2 antibody and wortmannin treatment significantly suppressed tumor growth, metastasis, and chemoresistance in mouse models. CONCLUSIONS: Our study demonstrated that the Id1/IGF2/PI3K/AKT signaling cascade plays an important role in esophageal cancer progression and chemoresistance. Blockade of IGF2/PI3K/AKT signaling has therapeutic potential in the management of esophageal cancer.-
dc.languageengen_US
dc.publisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/ejca-
dc.relation.ispartofEuropean Journal of Canceren_US
dc.subjectMedical sciences-
dc.subjectOncology-
dc.titleId1/IGF2/IGF1R/PI3K/AKT signaling cascade as functional markers and therapeutic targets in esophageal canceren_US
dc.typeConference_Paperen_US
dc.identifier.emailLi, B: libinhku@hkucc.hku.hken_US
dc.identifier.emailTsao, G: gswtsao@hku.hken_US
dc.identifier.emailChan, K: hrmtckw@hku.hken_US
dc.identifier.emailCheung, A: lmcheung@hku.hken_US
dc.identifier.authorityTsao, G=rp00399en_US
dc.identifier.hkuros226964en_US
dc.identifier.volume49en_US
dc.identifier.issuesuppl. 4-
dc.identifier.spageS23, abstract no. MC13-0039en_US
dc.identifier.epageS23, abstract no. MC13-0039en_US
dc.publisher.placeUnited Kingdom-

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