Evaluation of the novel gene Rabl3 in the regulation of proliferation and motility in human cancer cells.
Rab is a large subfamily of small GTPases which play an important role in multiple processes relating to cellular transportation and modulation of the cytoskeleton. Novel gene Rab-like 3 (Rabl3), which we originally reported as a new member belonging to this subfamily, may participate in other processes in human cancer cell lines based on our research. In order to investigate the function of Rabl3 and the basic mechanism which regulates cancer cell survival and motility, we constructed the Rabl3-pcDNA3.1 fusion plasmid, also, the specific siRNA against Rabl3 was used. We detected cellular viability and motility changes in Rabl3 overexpressed or si-Rabl3 transfected cancer cell lines. Overexpression of Rabl3 resulted in the enhancement of cell proliferation, inhibition of apoptosis and paclitaxel resistance in human cancer cell lines. Rabl3 also promoted cell motility activity. Next, we silenced Rabl3 in order to determine its exact physiological function. We found that processes which are associated with tumor formation and metastasis were inhibited. These included an increased incidence of apoptosis, abrogated cellular proliferation and mobility. Furthermore, western blot analysis revealed that the function of Rabl3 was closely associated with focal adhesion kinase (FAK) phosphorylation, both in HeLa and MDA-MB-231 cell lines at the sites of Tyr 397/576/577. Our results suggested that Rabl3 may be a novel oncogene which regulates the oncological behavior of human cancer cells. As a consequence, Rabl3 can be considered as a novel candidate in the control of tumorigenesis and as a new target for anti-tumor treatment.
Li
Qi
Q
Laboratory of Medical Immunology, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, PR China.
Wang
Li
L
Zeng
Linge
L
Zhang
Yingmei
Y
Li
Kangqi
K
Jin
Peng
P
Su
Bingnan
B
Wang
Lu
L
D000595:Amino Acid Sequence; D001483:Base Sequence; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D018922:HL-60 Cells; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology; D010802:Phylogeny; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D020691:rab GTP-Binding Proteins / Q000032:analysis / Q000235:genetics*
D034741:RNA, Small Interfering; C553331:Rabl3 protein, human; D020691:rab GTP-Binding Proteins; D017239:Paclitaxel