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Title: Targeting ILK and {beta}4 integrin abrogates the invasive potential of ovarian cancer

Abstract

Highlights: Black-Right-Pointing-Pointer The potential of targeting ILK and integrins for highly aggressive ovarian cancer. Black-Right-Pointing-Pointer Unanticipated synergistic effect for the combination of ILK/{beta}4 integrin. Black-Right-Pointing-Pointer Combination of ILK/{beta}4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. Black-Right-Pointing-Pointer Targeting of {beta}4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of {beta}1 and {beta}4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of {beta}1 and {beta}4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of {beta}4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK ormore » combination depletion of {beta}4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting {beta}4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.« less

Authors:
;  [1];  [2]; ;  [3];  [1];  [2]
  1. BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of)
  2. (Korea, Republic of)
  3. Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of)
Publication Date:
OSTI Identifier:
22210310
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 427; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; CELL PROLIFERATION; IN VITRO; IN VIVO; MOLECULES; NEOPLASMS; PHOSPHORYLATION; POLYMERASE CHAIN REACTION

Citation Formats

Choi, Yoon Pyo, Kim, Baek Gil, Department of Pathology, Yonsei University College of Medicine, Seoul, Gao, Ming-Qing, Kang, Suki, Cho, Nam Hoon, E-mail: cho1988@yuhs.ac, and Department of Pathology, Yonsei University College of Medicine, Seoul. Targeting ILK and {beta}4 integrin abrogates the invasive potential of ovarian cancer. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2012.09.114.
Choi, Yoon Pyo, Kim, Baek Gil, Department of Pathology, Yonsei University College of Medicine, Seoul, Gao, Ming-Qing, Kang, Suki, Cho, Nam Hoon, E-mail: cho1988@yuhs.ac, & Department of Pathology, Yonsei University College of Medicine, Seoul. Targeting ILK and {beta}4 integrin abrogates the invasive potential of ovarian cancer. United States. doi:10.1016/J.BBRC.2012.09.114.
Choi, Yoon Pyo, Kim, Baek Gil, Department of Pathology, Yonsei University College of Medicine, Seoul, Gao, Ming-Qing, Kang, Suki, Cho, Nam Hoon, E-mail: cho1988@yuhs.ac, and Department of Pathology, Yonsei University College of Medicine, Seoul. Fri . "Targeting ILK and {beta}4 integrin abrogates the invasive potential of ovarian cancer". United States. doi:10.1016/J.BBRC.2012.09.114.
@article{osti_22210310,
title = {Targeting ILK and {beta}4 integrin abrogates the invasive potential of ovarian cancer},
author = {Choi, Yoon Pyo and Kim, Baek Gil and Department of Pathology, Yonsei University College of Medicine, Seoul and Gao, Ming-Qing and Kang, Suki and Cho, Nam Hoon, E-mail: cho1988@yuhs.ac and Department of Pathology, Yonsei University College of Medicine, Seoul},
abstractNote = {Highlights: Black-Right-Pointing-Pointer The potential of targeting ILK and integrins for highly aggressive ovarian cancer. Black-Right-Pointing-Pointer Unanticipated synergistic effect for the combination of ILK/{beta}4 integrin. Black-Right-Pointing-Pointer Combination of ILK/{beta}4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. Black-Right-Pointing-Pointer Targeting of {beta}4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of {beta}1 and {beta}4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of {beta}1 and {beta}4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of {beta}4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of {beta}4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting {beta}4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.},
doi = {10.1016/J.BBRC.2012.09.114},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 427,
place = {United States},
year = {2012},
month = {10}
}