Depleting MEKK1 expression inhibits the ability of invasion and migration of human pancreatic cancer cells.
BACKGROUND
Mitogen-activated protein/ERK kinase 1 (MEKK1) is a Ser/Thr protein kinase belonging to the MEKK/STE11 subgroup of the MAPKKK family and plays a key role in tumor metastasis. However, it remains unclear about its functions in pancreatic cancer.


METHODS
We analyzed MEKK1 expression in 41 surgically resection pancreatic cancer patient's samples by immunohistochemistry and determined its role in BxPC3 cells via RNAi experiment. The abilities of invasion, motility, and adhesion of BxPC3 cells were detected by transwell assay, wound healing assay and adhesion assay, respectively. Gelatinase activity of MMPs in cultured cells was examined by gelatin zymography.


RESULTS
Our data showed that MEKK1 expression is positively correlated with lymphatic metastases (P < 0.01). The abilities of invasion, motility, and adhesion of BxPC3 cells were inhibited significantly (P < 0.01) when MEKK1 was depleted with a specific siRNA. We observed that the activity of MMP2 was decreased in the MEKK1 depletion cell line (P < 0.05), accompanied with decreased phosphorylated ERK1/2.


CONCLUSIONS
Our results indicated that the depletion of MEKK1 led to a potent inhibition on the invasion and migration of human pancreatic adenocarcinoma in vitro. It suggests that MEKK1 may be a potential target for development of anti-invasion and metastasis drugs.
Su
Fuqin
F
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, 100050, Beijing, China.
Li
Hongyan
H
Yan
Chaoqi
C
Jia
Baoqing
B
Zhang
Yi
Y
Chen
Xiaoguang
X
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1 / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D034741:RNA, Small Interfering / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D034741:RNA, Small Interfering; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human