DOCK2 regulates cell proliferation through Rac and ERK activation in B cell lymphoma.
DOCK2; a member of the CDM protein family, regulates cell motility and cytokine production through the activation of Rac in mammalian hematopoietic cells and plays a pivotal role in the modulation of the immune system. Here we demonstrated the alternative function of DOCK2 in hematopoietic tumor cells, especially in terms of its association with the tumor progression. Immunostaining for DOCK2 in 20 cases of human B cell lymphoma tissue specimens including diffuse large B cell lymphoma and follicular lymphoma revealed the prominent expression of DOCK2 in all of the lymphoma cells. DOCK2-knockdown (KD) of the B cell lymphoma cell lines, Ramos and Raji, using the lentiviral shRNA system presented decreased cell proliferation compared to the control cells. Furthermore, the tumor formation of DOCK2-KD Ramos cell in nude mice was significantly abrogated. Western blotting analysis and pull-down assay using GST-PAK-RBD kimeric protein suggested the presence of DOCK2-Rac-ERK pathway regulating the cell proliferation of these lymphoma cells. This is the first report to clarify the prominent role of DOCK2 in hematopoietic malignancy.
Wang
Lei
L
Laboratory of Cancer Research, Department of Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kitaku, Sapporo 060-8638, Japan.
Nishihara
Hiroshi
H
Kimura
Taichi
T
Kato
Yasutaka
Y
Tanino
Mishie
M
Nishio
Mitsufumi
M
Obara
Masato
M
Endo
Tomoyuki
T
Koike
Takao
T
Tanaka
Shinya
S
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D055785:Gene Knockdown Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology*; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
C402110:DOCK2 protein, human; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases