Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells.
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.
Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA.
Jin
J
Dai
Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA.
Peter G
PG
Van Wie
Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA.
Leonard Yenwong
LY
Fai
Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA.
Donghern
D
Kim
Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536, USA.
Lei
L
Wang
Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536, USA.
Pratheeshkumar
P
Poyil
Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA.
Jia
J
Luo
Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA. Electronic address: Zhuo.Zhang@uky.edu.
Zhuo
Z
Zhang
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C099942:NEDD9 protein, human; D010750:Phosphoproteins; D047310:Apigenin; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt
Apigenin; Colorectal cancer; Invasion; Metastasis; Migration; NEDD9
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