Extracellular signal-regulated kinase 8-mediated c-Jun phosphorylation increases tumorigenesis of human colon cancer.
Extracellular signal-regulated kinase 8 (ERK8), a recently discovered member of the mitogen-activated protein kinase protein family, has been less studied than other family members, leaving its physiologic functions mostly unknown. The biological consequences of overexpression of ERK8 in JB6 Cl41 epidermal skin cells or knockdown of ERK8 in HCT15 colorectal cancer cells was studied. Kinase assays and transient transfection experiments were performed to study the signaling pathway between ERK8 and c-Jun. We found that ERK8 is relatively highly expressed in HCT15 human colorectal cancer cells and plays an important role in the promotion and progression of colorectal cancer. ERK8 promoted neoplastic transformation, and knockdown of ERK8 in HCT15 colorectal cancer cells reduced the tumorigenic properties of these cell lines. Furthermore, a direct interaction between ERK8 and c-Jun was shown. With epidermal growth factor treatment, overexpression of ERK8 in JB6 Cl41 cells caused an increased phosphorylation of c-Jun at Ser(63) and Ser(73), resulting in increased activator protein-1 transactivation. In contrast, knockdown of ERK8 in HCT15 colorectal cancer cells blocked c-Jun phosphorylation. The interaction between ERK8 and c-Jun seems to increase the tumorigenic properties of HCT15 colorectal cancer cells. Thus, ERK8-regulated signaling might serve as a potential therapeutic target in colorectal cancer.
Xu
Yan-Ming
YM
The Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.
Zhu
Feng
F
Cho
Yong-Yeon
YY
Carper
Andria
A
Peng
Cong
C
Zheng
Duo
D
Yao
Ke
K
Lau
Andy T Y
AT
Zykova
Tatyana A
TA
Kim
Hong-Gyum
HG
Bode
Ann M
AM
Dong
Zigang
Z
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000201:enzymology*; D018450:Disease Progression; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000378:metabolism; D012694:Serine / Q000737:chemistry
D034741:RNA, Small Interfering; D012694:Serine; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C456320:MAPK15 protein, human