CRISPR/Cas9 engineering of ERK5 identifies its FAK/PYK2 dependent role in adhesion-mediated cell survival

Ali, Moazzam; Mutahir, Zeeshan; Riaz, Anjum

doi:10.1016/j.bbrc.2019.03.145

Cited by 6 publications

(4 citation statements)

References 46 publications

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“…We discovered cell extrinsic effects of ERK5 deletion on the tumor microenvironment, specifically extracellular matrix composition and fiber alignment. ERK5-deficient TNBC cells have been shown to reduce cell attachment to matrix proteins fibronectin and vitronectin through FAK/PYK2-mediated signaling (55). Our data supports these findings, with ERK5 depletion resulting in loss of key extracellular matrix proteins essential for the adherence of integrins (44,56) through suppressed expression of integrin alpha subunits (ITGA) 1, 2, 10, and 11.…”

Section: Discussionsupporting

confidence: 84%

ERK5 Is Required for Tumor Growth and Maintenance Through Regulation of the Extracellular Matrix in Triple Negative Breast Cancer

et al. 2020

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Section: Discussionsupporting

confidence: 84%

ERK5 Is Required for Tumor Growth and Maintenance Through Regulation of the Extracellular Matrix in Triple Negative Breast Cancer

et al. 2020

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“…In fact, we were able to detect a potent expression of this MAPK in a short series of rhabdomyosarcomas, indicating that further study is necessary to assess whether our observation is restricted to sarcoma of the muscular origin or can also be extrapolated to other sarcomatous pathologies. Regarding cell proliferation, although some reports suggest a lack of implication of ERK5 [ 50 , 51 , 52 ], our results obtained in growth curves and foci assays reinforce the critical role of this MAPK in cell proliferation and survival, as it has been previously described [ 27 , 49 , 53 ]. However, we cannot discard that cell type/genetic background issues, as well as different methodological approaches, could be critical to explaining the discrepancy between the different reports.…”

Section: Discussionsupporting

confidence: 90%

ERK5 Is a Major Determinant of Chemical Sarcomagenesis: Implications in Human Pathology

Arconada-Luque

Jiménez-Suarez

Pascual-Serra

et al. 2022

Cancers

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Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma. Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq showed a deregulated gene expression pattern for key biological processes such as angiogenesis, migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5 as indicated by its specific interference, demonstrating that the ERK5–KLF2 axis is an important determinant of sarcoma biology that should be further studied in human pathology.

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“…Interestingly, it has been demonstrated that ERK5-signaling suppression in TNBC and PC-3 cell lines lead to a drastic decrease in FAK phosphorylation, motility, and cell adhesion [ 93 ]. In accordance, recent studies have further underlined the critical linkage between the MEK5/ERK5 axis and the maintenance of the invasive capability of TNBC [ 94 , 95 ], LC, and melanoma [ 96 ] through FAK activation. Additionally, it has been found that ERK5 mainly localizes in the cytoplasm and membrane of ERα-negative BC cells, promoting actin remodeling, cell mobility, and invasion [ 97 ].…”

Section: Introductionmentioning

confidence: 61%

Clinical Significance and Regulation of ERK5 Expression and Function in Cancer

Monti

Celli

Missale

et al. 2022

Cancers

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Extracellular signal-regulated kinase 5 (ERK5) is a unique kinase among MAPKs family members, given its large structure characterized by the presence of a unique C-terminal domain. Despite increasing data demonstrating the relevance of the ERK5 pathway in the growth, survival, and differentiation of normal cells, ERK5 has recently attracted the attention of several research groups given its relevance in inflammatory disorders and cancer. Accumulating evidence reported its role in tumor initiation and progression. In this review, we explore the gene expression profile of ERK5 among cancers correlated with its clinical impact, as well as the prognostic value of ERK5 and pERK5 expression levels in tumors. We also summarize the importance of ERK5 in the maintenance of a cancer stem-like phenotype and explore the major known contributions of ERK5 in the tumor-associated microenvironment. Moreover, although several questions are still open concerning ERK5 molecular regulation, different ERK5 isoforms derived from the alternative splicing process are also described, highlighting the potential clinical relevance of targeting ERK5 pathways.

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CRISPR/Cas9 engineering of ERK5 identifies its FAK/PYK2 dependent role in adhesion-mediated cell survival

Cited by 6 publications

References 46 publications

ERK5 Is Required for Tumor Growth and Maintenance Through Regulation of the Extracellular Matrix in Triple Negative Breast Cancer

ERK5 Is Required for Tumor Growth and Maintenance Through Regulation of the Extracellular Matrix in Triple Negative Breast Cancer

ERK5 Is a Major Determinant of Chemical Sarcomagenesis: Implications in Human Pathology

Clinical Significance and Regulation of ERK5 Expression and Function in Cancer

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