TM4SF4 overexpression in radiation-resistant lung carcinoma cells activates IGF1R via elevation of IGF1

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Title
TM4SF4 overexpression in radiation-resistant lung carcinoma cells activates IGF1R via elevation of IGF1
Author(s)
S I Choi; S Y Kim; J Lee; Eun Wie Cho; I G Kim
Bibliographic Citation
Oncotarget, vol. 5, no. 20, pp. 9823-9837
Publication Year
2014
Abstract
Transmembrane 4 L six family member 4 (TM4SF4) is a member of the tetraspanin L6 domain family. Other members of this family, TM4SF1 (also known as L6-Ag) and TM4SF5, have been shown to be upregulated in multiple tumors and involved in epithelial-to-mesenchymal transition and cell migration. However, unlike its homologs, little is known about TM4SF4. Here, we show that TM4SF4 was highly expressed in radiation-resistant lung adenocarcinoma cells, such as A549 and Calu-3 cells, and its expression activated cell growth, migration, and invasion. Overexpression of TM4SF4 in A549 cells increased the activation of PI3K, AKT, and NF-kappaB and the expression of PTEN. IGF1R was clearly activated by overexpression of TM4SF4, although EGFR was also slightly activated. TM4SF4 expression was correlated with the increased expression of IGF1, consequently resulting in IGF1R activation. Tumorigenic activity of TM4SF4 in lung adenocarcinoma cells was also demonstrated by xenograft assay; however, this activity was almost completely suppressed by treatment with anti-TM4SF4 antibody. Our results suggest that TM4SF4 overexpression in lung carcinoma cells results in resistance to radiotherapy via IGF1-induced IGF1R activation and blocking the activity of TM4SF4 using specific antibody can be a promising therapeutics against TM4SF4-overexpressing lung adenocarcinoma.
Keyword
IGF1IGF1R activationLung adenocarcinomaTM4SF4
ISSN
1949-2553
Publisher
Impact Journals
DOI
http://dx.doi.org/10.18632/oncotarget.2450
Type
Article
Appears in Collections:
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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