Activation of the Integrin Effector Kinase Focal Adhesion Kinase in Cancer Cells Is Regulated by Crosstalk between Protein Kinase Cα and the PDZ Adapter Protein mda-9/Syntenin

Hwangbo, Cheol; Kim, Jae‐Kyung; Lee, Jun Young; Lee, Jeong‐Hyung

doi:10.1158/0008-5472.can-09-2447

Cited by 72 publications

(72 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Plasmids and RNA Interference-Expression vectors for FLAG-tagged mda-9/syntenin, PKC␣, the dominant negative (DN)-PKC␣, and DN-Rac1 were described previously (15). Expression vectors for the FLAG-Akt, DN-Akt, and DN-PI3K were obtained from Dr. N. Fujita (Japanese Foundation for Cancer Research, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…All constructs and mutations were confirmed by DNA sequencing. The pSUPER shRNA-producing plasmids (pSUPER/syntenin and pSUPER-scramble) were previously described (15). siRNAs for mda-9/syntenin, ILK and scramble control were from Santa Cruz Biotechnology.…”

Section: Methodsmentioning

confidence: 99%

“…mda-9/syntenin may interact directly with c-Src, and this interaction correlates with increased formation of active FAK-c-Src signaling complexes (12,13), which are important for regulation of migration machinery (14). We recently showed that transient induction of mda-9/syntenin during adhesion to FN is dependent on PKC␣ activation and enhances the FN-induced assembly of integrin ␤1 signaling complexes with FAK and c-Src, activating FAK and its downstream pathways (15). The role of mda-9/syntenin in regulation of signaling of extracellular matrices other than FN has not been well elucidated.…”

Section: Pdzmentioning

confidence: 99%

See 2 more Smart Citations

mda-9/Syntenin Protein Positively Regulates the Activation of Akt Protein by Facilitating Integrin-linked Kinase Adaptor Function during Adhesion to Type I Collagen

Hwangbo

Park

Lee

2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background:We investigated the role of mad-9/syntenin, a cancer metastasis inducer, in ILK adaptor function during adhesion to type I collagen. Results: mda-9/syntenin positively regulates the scaffold function of ILK. Conclusion: mda-9/syntenin regulates the activation of ILK signaling molecules by facilitating ILK adaptor function during adhesion to type I collagen. Significance: We describe a new mechanism of mda-9/syntenin for regulation of cancer metastasis.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Pdzmentioning

confidence: 99%

See 1 more Smart Citation

mda-9/Syntenin Protein Positively Regulates the Activation of Akt Protein by Facilitating Integrin-linked Kinase Adaptor Function during Adhesion to Type I Collagen

Hwangbo

Park

Lee

2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Previous studies have indicated that TM4SF1 is associated with poor prognosis in squamous lung carcinoma (21) and mesothelioma (22). In addition, TM4SF1 combines with synthenin-2, which promotes melanoma and breast-cancer metastasis by activating protein kinase C and focal adhesion kinase/Src family kinase signaling (23)(24)(25).…”

Section: A Gain-of-function Platform For the Identification Of Canonimentioning

confidence: 99%

Forward genetic screens in mice uncover mediators and suppressors of metastatic reactivation

Gao

Chakraborty²,

Lee-Lim³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

We have developed a screening platform for the isolation of genetic entities involved in metastatic reactivation. Retroviral libraries of cDNAs from fully metastatic breast-cancer cells or pooled microRNAs were transduced into breast-cancer cells that become dormant upon infiltrating the lung. Upon inoculation in the tail vein of mice, the cells that had acquired the ability to undergo reactivation generated metastatic lesions. Integrated retroviral vectors were recovered from these lesions, sequenced, and subjected to a second round of validation. By using this strategy, we isolated canonical genes and microRNAs that mediate metastatic reactivation in the lung. To identify genes that oppose reactivation, we screened an expression library encoding shRNAs, and we identified target genes that encode potential enforcers of dormancy. Our screening strategy enables the identification and rapid biological validation of single genetic entities that are necessary to maintain dormancy or to induce reactivation. This technology should facilitate the elucidation of the molecular underpinnings of these processes.forward genetic screens | metastatic reactivation | cDNA library screen | shRNA library screen | microRNA library screen T he majority of cancer-related deaths are caused by metastatic relapse (1). The process through which cancer cells acquire metastatic capacity is complex. Unrestrained proliferation, resistance to proapoptotic insults, and invasion through tissue boundaries are not sufficient for metastasis. To colonize distant organs, cancer cells must also adapt to the local microenvironment of the target organ and finally outgrow (2, 3). Mathematical modeling of clinical data and experiments in mouse models suggest that cancer cells disseminating from prevalent cancers, such as those of the breast and prostate, undergo an extended period of dormancy at premetastatic sites (4). Insights into the mechanisms that enable disseminated cancer cells to survive during dormancy and then outgrow into life-threatening lesions may lead to the identification of novel therapeutic targets for the prevention or treatment of metastatic disease.Advances in genomics and mouse modeling have fostered a renaissance of studies on metastasis (2, 3). Current approaches to the study of metastasis can be divided in two categories. In the first, genetic methods are used to modify the function of a candidate gene in intact mice or in cells that are subsequently transplanted in mice (5, 6). In the second, genomic methods, such as DNA microarray analysis or array comparative genomic hybridization (aCGH), are used to identify a restricted number of candidate genes, which are then tested in appropriate mouse models (7,8). Although these approaches have been extremely successful, they are very laborious and do not necessarily yield biologically potent mediators of metastasis. Functional genetic screens can lead to the rapid identification of strong mediators of a selectable phenotype (9, 10). In agreement with this notion, recent studies have ...

show abstract

“…Integrin was reported to regulate EMT via focal adhesion kinase (FAK) (23) or integrin linked kinase (ILK) (24). The signaling of PI3K/AKT (25), WNT (26), and rAS/mAPK (27) are all downstream targets of integrin signaling. Members of the Rho GTPase family are mainly involved in the regulation of cytoskeletal and cell adhesion (28); RhoGDI is an important negative regulator of Rho GTPase.…”

Section: Discussionmentioning

confidence: 99%

Sustainable inflammation transforms hepatic cells by causing oxidative stress injury and potential epithelial-mesenchymal transition

Lü

Liu

Yang

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. The inflammatory microenvironment promotes tumorigenesis. However, the mechanism through which inflammation transforms hepatic cells in precancerous lesions remains unclear. Hepatic cells undergo significant changes in metabolism before carcinogenesis, but the specific alterations in gene expression and cellular functions in response to precancerous inflammation have not been elucidated. In this study, a hepatitis-hepatoma mouse model was successfully established. Label-free quantitative (LFQ) proteomics coupled with bioinformatics analysis was then performed to identify differentially expressed proteins and their functions in hepatic cells with precancerous inflammation. We found that different chemical treatments induced several common changes in the model. Hepatic cells underwent serious oxidative stress injury. Canonical pathway analysis using IPA revealed the activation of signaling pathways, such as integrin signaling, signaling by Rho family GTPases, IL-8 signaling, and ILK signaling, as well as the inhibition of RhoGDI signaling. Analysis of the KEGG pathway indicated alteration in the pathways for focal adhesion and regulation of actin cytoskeleton. Results from western blot analysis demonstrated the upregulation of proteins, including p-STAT3, TWIST, SNAIL, Vimentin, and MMP-9, which are involved in epithelial-mesenchymal transition (EMT). These results indicated that hepatic cells were likely to undergo EMT. Interestingly, the expression of E-cadherin was upregulated, but this observation must be further investigated. In conclusion, the results revealed that notable functional and pathway changes occurred during the precancerous inflammation stage in the liver. Our study contributes to understanding of the roles of inflammation in tumorigenesis and provides a molecular basis for further studies on the tumorigenesis of hepatocellular carcinoma.

show abstract

Activation of the Integrin Effector Kinase Focal Adhesion Kinase in Cancer Cells Is Regulated by Crosstalk between Protein Kinase Cα and the PDZ Adapter Protein mda-9/Syntenin

Cited by 72 publications

References 40 publications

mda-9/Syntenin Protein Positively Regulates the Activation of Akt Protein by Facilitating Integrin-linked Kinase Adaptor Function during Adhesion to Type I Collagen

mda-9/Syntenin Protein Positively Regulates the Activation of Akt Protein by Facilitating Integrin-linked Kinase Adaptor Function during Adhesion to Type I Collagen

Forward genetic screens in mice uncover mediators and suppressors of metastatic reactivation

Sustainable inflammation transforms hepatic cells by causing oxidative stress injury and potential epithelial-mesenchymal transition

Contact Info

Product

Resources

About