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Title: Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells

Abstract

Apigenin is a natural flavonoid which possesses multiple anti-cancer properties such as anti-proliferation, anti-inflammation, and anti-metastasis in many types of cancers including colorectal cancer. Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a multi-domain scaffolding protein of the Cas family which has been shown to correlate with cancer metastasis and progression. The present study investigates the role of NEDD9 in apigenin-inhibited cell migration, invasion, and metastasis of colorectal adenocarcinoma DLD1 and SW480 cells. The results show that knockdown of NEDD9 inhibited cell migration, invasion, and metastasis and that overexpression of NEDD9 promoted cell migration and invasion of DLD1 cells and SW4890 cells. Apigenin treatment attenuated NEDD9 expression at protein level, resulting in reduced phosphorylations of FAK, Src, and Akt, leading to inhibition on cell migration, invasion, and metastasis of both DLD1 and SW480 cells. The present study has demonstrated that apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt cascade in colorectal cancer cells. NEDD9 may function as a biomarker for evaluation of cancer aggressiveness and for selection of therapeutic drugs against cancer progression. - Highlights: • Apigenin inhibits migration, invasion, and metastasis of colorectal cancer cells. • Apigenin downregulates NEDD9. • Apigenin decreases phosphorylations of FAK, Src, andmore » Akt. • Apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt.« less

Authors:
; ; ;  [1]; ;  [2];  [3];  [1]
  1. Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536 (United States)
  2. Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States)
  3. Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536 (United States)
Publication Date:
OSTI Identifier:
22690854
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 311; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOLOGICAL MARKERS; CARCINOMAS; DRUGS; EVALUATION; FLAVONOIDS; INFLAMMATION; INHIBITION; METASTASES; PHOSPHORYLATION; PRECURSOR; PROTEINS

Citation Formats

Dai, Jin, Van Wie, Peter G., Fai, Leonard Yenwong, Kim, Donghern, Wang, Lei, Poyil, Pratheeshkumar, Luo, Jia, and Zhang, Zhuo. Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells. United States: N. p., 2016. Web. doi:10.1016/J.TAAP.2016.09.016.
Dai, Jin, Van Wie, Peter G., Fai, Leonard Yenwong, Kim, Donghern, Wang, Lei, Poyil, Pratheeshkumar, Luo, Jia, & Zhang, Zhuo. Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells. United States. doi:10.1016/J.TAAP.2016.09.016.
Dai, Jin, Van Wie, Peter G., Fai, Leonard Yenwong, Kim, Donghern, Wang, Lei, Poyil, Pratheeshkumar, Luo, Jia, and Zhang, Zhuo. Tue . "Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells". United States. doi:10.1016/J.TAAP.2016.09.016.
@article{osti_22690854,
title = {Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells},
author = {Dai, Jin and Van Wie, Peter G. and Fai, Leonard Yenwong and Kim, Donghern and Wang, Lei and Poyil, Pratheeshkumar and Luo, Jia and Zhang, Zhuo},
abstractNote = {Apigenin is a natural flavonoid which possesses multiple anti-cancer properties such as anti-proliferation, anti-inflammation, and anti-metastasis in many types of cancers including colorectal cancer. Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a multi-domain scaffolding protein of the Cas family which has been shown to correlate with cancer metastasis and progression. The present study investigates the role of NEDD9 in apigenin-inhibited cell migration, invasion, and metastasis of colorectal adenocarcinoma DLD1 and SW480 cells. The results show that knockdown of NEDD9 inhibited cell migration, invasion, and metastasis and that overexpression of NEDD9 promoted cell migration and invasion of DLD1 cells and SW4890 cells. Apigenin treatment attenuated NEDD9 expression at protein level, resulting in reduced phosphorylations of FAK, Src, and Akt, leading to inhibition on cell migration, invasion, and metastasis of both DLD1 and SW480 cells. The present study has demonstrated that apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt cascade in colorectal cancer cells. NEDD9 may function as a biomarker for evaluation of cancer aggressiveness and for selection of therapeutic drugs against cancer progression. - Highlights: • Apigenin inhibits migration, invasion, and metastasis of colorectal cancer cells. • Apigenin downregulates NEDD9. • Apigenin decreases phosphorylations of FAK, Src, and Akt. • Apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt.},
doi = {10.1016/J.TAAP.2016.09.016},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = ,
volume = 311,
place = {United States},
year = {2016},
month = {11}
}