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

Jin Dai; Peter G Van Wie; Leonard Yenwong Fai; Donghern Kim; Lei Wang; Pratheeshkumar Poyil; Jia Luo; Zhuo Zhang

doi:10.1016/j.taap.2016.09.016

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

Journal article

Open access

Peer reviewed

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

Jin Dai, Peter G Van Wie, Leonard Yenwong Fai, Donghern Kim, Lei Wang, Pratheeshkumar Poyil, Jia Luo and Zhuo Zhang

Toxicology and applied pharmacology, Vol.311, pp.106-112

11/15/2016

DOI: 10.1016/j.taap.2016.09.016

PMCID: PMC5759047

PMID: 27664007

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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.

Adaptor Proteins, Signal Transducing - metabolism

Animals

Apigenin - pharmacology

Cell Line, Tumor

Colorectal Neoplasms - metabolism

Colorectal Neoplasms - pathology

Down-Regulation - drug effects

Female

Focal Adhesion Protein-Tyrosine Kinases - metabolism

Humans

Mice

Mice, Nude

Neoplasm Invasiveness

Neoplasm Metastasis

Phosphoproteins - metabolism

Phosphorylation

Proto-Oncogene Proteins c-akt - metabolism

Signal Transduction

src-Family Kinases - metabolism

Details

Title: Subtitle: Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells
Creators: Jin Dai - University of Kentucky
Peter G Van Wie - University of Kentucky
Leonard Yenwong Fai - University of Kentucky
Donghern Kim - University of Kentucky
Lei Wang - University of Kentucky
Pratheeshkumar Poyil - University of Kentucky
Jia Luo - University of Kentucky
Zhuo Zhang - University of Kentucky
Resource Type: Journal article
Publication Details: Toxicology and applied pharmacology, Vol.311, pp.106-112
DOI: 10.1016/j.taap.2016.09.016
PMID: 27664007
PMCID: PMC5759047
NLM abbreviation: Toxicol Appl Pharmacol
ISSN: 0041-008X
eISSN: 1096-0333
Grant note: P30 CA177558 / NCI NIH HHS R01 AA017226 / NIAAA NIH HHS
Language: English
Date published: 11/15/2016
Academic Unit: Pathology
Record Identifier: 9984201117302771

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