DGCR6L, a novel PAK4 interaction protein, regulates PAK4-mediated migration of human gastric cancer cell via LIMK1

Li, Xiaodong; Ke, Qingen; Li, Yanshu; Liu, Funan; Zhu, Gangjie; Li, Feng

doi:10.1016/j.biocel.2009.09.008

Cited by 58 publications

(48 citation statements)

References 34 publications

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“…Previous studies have demonstrated that group II PAK activity can influence cancer-cell behavior [31] . PAK4 is closely associated with the progression and metastasis of breast cancer [32] , the adhesion of prostate cancer cells [33] and the migration of human gastric cancer cells [34] , and PAK6 is overexpressed in prostate cancer and breast cancer cell lines [29,35] . Several studies have provided detailed insights into the role of the PAK5 protein in colorectal cancer [15,16] and pancreatic [17] .…”

Section: Discussionmentioning

confidence: 99%

P21-activated kinase 5 plays essential roles in the proliferation and tumorigenicity of human hepatocellular carcinoma

Fang¹,

Jiang

et al. 2013

Acta Pharmacol Sin

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Aim: To investigate the roles of P21-activated kinase 5 (PAK5) in proliferation and tumorigenicity of human hepatocellular carcinoma (HCC). Methods: HCC and matched paraneoplastictis tissue samples were obtained from 30 patients. Human HCC cell lines SMMC7721, HepG2, Hep3B, SK-HEP-1, Huh-7, and liver cell line HL-7702 were examined. The expression of PAK5 gene was studied using real-time qPCR and Western blotting. Cell proliferation was quantified with the MTT assay. Cell cycle was analyzed with flow cytometry. The tumorigenicity of Lv-shRNA-transfected HepG2 cells was evaluated in BALB/cA nude mice. Results: The mRNA level of PAK5 was significantly higher in 25 out of 30 HCC samples compared to the matched paraneoplastic tissues. The HCC cell lines showed varying expression of PAK5 protein, and the highest level was found in the HepG2 cells. PAK5 gene silencing in HepG2 cells markedly reduced the cell proliferation and colony formation, and induced cell cycle arrest in the G 1 phase. Furthermore, PAK5 gene silencing suppressed the tumor formation in nude mice, and significantly decreased the expression of HCCrelated genes Cyclin D1 and beta-catenin. Conclusion: PAK5 may play essential roles in the initiation and progression of human HCC. Thus, it may be an effective therapeutic target or perhaps serve as a clinical diagnostic or prognostic marker in human HCC.

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Section: Discussionmentioning

confidence: 99%

P21-activated kinase 5 plays essential roles in the proliferation and tumorigenicity of human hepatocellular carcinoma

Fang¹,

Jiang

et al. 2013

Acta Pharmacol Sin

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“…Cofilin is hypothesized to drive migration by depolymerizing F-actin [44]. It was reported earlier that LIMK phosphorylation of cofilin might inactivate cofilin by preventing its binding to F-actin filaments and this inactivation is predicted to inhibit cell migration [45], but recent data indicated that phosphorylation of cofilin is essential for establishing directed cell protrusion [46] and cell migration also requires cofilin phosphorylation step which is mediated by PAK4 [47]. Further studies are needed to elucidate the mechanism by which cecropinXJ affects the migration and invasion of esophageal cancer cells.…”

Section: Discussionmentioning

confidence: 99%

CecropinXJ, a silkworm antimicrobial peptide, induces cytoskeleton disruption in esophageal carcinoma cells

Li¹,

Wu²,

Kang³

et al. 2014

ABBS

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Antimicrobial peptides exist in the non-specific immune system of organism and participate in the innate host defense of each species. CecropinXJ, a cationic antimicrobial peptide, possesses potent anticancer activity and acts preferentially on cancer cells instead of normal cells, but the mechanism of cancer cell death induced by cecropinXJ remains largely unknown. This study was performed to investigate the cytoskeleton-disrupting effects of cecropinXJ on human esophageal carcinoma cell line Eca109 using scanning electron microscopy observation, fluorescence imaging, cell migration and invasion assays, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. The electronic microscope and fluorescence imaging observation suggested that cecropinXJ could result in morphological changes and induce damage to microtubules and actin of Eca109 cells in a dose-dependent manner. The cell migration and invasion assays demonstrated that cecropinXJ could inhibit migration and invasion of tumor cells. Western blot and qRT-PCR analysis showed that there was obvious correlation between microtubule depolymerization and actin polymerization induced by cecropinXJ. Moreover, cecropinXJ might also cause decreased expression of a-actin, b-actin, g-actin, a-tubulin, and b-tubulin genes in concentration-and time-dependent manners. In summary, this study indicates that cecropinXJ triggers cytotoxicity in Eca109 cells through inducing the cytoskeleton destruction and regulating the expression of cytoskeleton proteins. This cecropinXJ-mediated cytoskeleton-destruction effect is instrumental in our understanding of the detailed action of antimicrobial peptides in human cancer cells and cecropinXJ might be a potential therapeutic agent for the treatment of cancer in the future.

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“…DGCR6L binds to PAK4, and this interaction enhances LIMK phosphorylation, leading to increased migration of gastric cells. 45 Filamin A (FLNa) is another cytoskeletal regulatory protein that is targeted by the Paks. 46 FLNa is an actin binding protein which connects actin filaments to the cell membrane.…”

Section: Pak Kinases and Cytoskeletal Organizationmentioning

confidence: 99%

P21 activated kinases

Rane¹,

Minden²

2014

Small GTPases

189

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DGCR6L, a novel PAK4 interaction protein, regulates PAK4-mediated migration of human gastric cancer cell via LIMK1

Cited by 58 publications

References 34 publications

P21-activated kinase 5 plays essential roles in the proliferation and tumorigenicity of human hepatocellular carcinoma

P21-activated kinase 5 plays essential roles in the proliferation and tumorigenicity of human hepatocellular carcinoma

CecropinXJ, a silkworm antimicrobial peptide, induces cytoskeleton disruption in esophageal carcinoma cells

P21 activated kinases

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