Can tumor cells proliferate without ERK5?

Giurisato, Emanuele; Tournier, Cathy

doi:10.1080/15384101.2016.1143272

Cited by 5 publications

(3 citation statements)

References 7 publications

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“…Other previous evidence demonstrated that MEK5/ERK5 overexpression elicits the proliferation of CC cells and that the activation of the CDK5-ERK5 axis is required for the growth of CRC cells [ 56 , 84 ]. The requirement of RAS for mediating ERK5 activation downstream of growth factor stimulation remains controversial [ 85 ]. It has been reported that in a set of CRC cell lines with oncogenic KRAS-BRAF or ERK5 amplification, ERK5 did not contribute to tumor proliferation and no evidence about the regulation of ERK5 by the mutated KRAS/BRAF signaling was observed [ 86 ].…”

Section: Introductionmentioning

confidence: 99%

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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Section: Introductionmentioning

confidence: 99%

Clinical Significance and Regulation of ERK5 Expression and Function in Cancer

Monti

Celli

Missale

et al. 2022

Cancers

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“…ERK5 is a relatively recently identified MAPK and displays different functions from MAPK family members. ERK5 activation mediated by RAS [5] has been associated with a diverse range of cellular processes including cell proliferation, migration, survival and angiogenesis [6]. Besides, activation of ERK5 in fibroblasts can lead to changes in the organization of actin cytoskeleton, including a loss of stress fibers [7] and formation of invasive adhesion structures termed podosomes [8].…”

Section: Introductionmentioning

confidence: 99%

Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer

Moncho-Amor

Pintado‐Berninches

Cáceres

et al. 2019

IJMS

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DUSP6/MKP3 is a dual-specific phosphatase that regulates extracellular regulated kinase ERK1/2 and ERK5 activity, with an increasingly recognized role as tumor suppressor. In silico studies from Gene expression Omnibus (GEO) and Cancer Genome atlas (TCGA) databases reveal poor prognosis in those Non-small cell lung cancer (NSCLC) patients with low expression levels of DUSP6. In agreement with these data, here we show that DUSP6 plays a major role in the regulation of cell migration, motility and tumor growth. We have found upregulation in the expression of several genes involved in epithelial to mesenchymal transition (EMT) in NSCLC-DUSP6 depleted cells. Data obtained in RNA-seq studies carried out in DUSP6 depleted cells identified EGFR, TGF-β and WNT signaling pathways and several genes such as VAV3, RUNXR2, LEF1, FGFR2 whose expression is upregulated in these cells and therefore affecting cellular functions such as integrin mediated cell adhesion, focal adhesion and motility. Furthermore, EGF signaling pathway is activated via ERK5 and not ERK1/2 and TGF-β via SMAD2/3 in DUSP6 depleted cells. In summary DUSP6 is a tumor suppressor in NSCLC and re-establishment of its expression may be a potential strategy to revert poor outcome in NSCLC patients.

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“…In addition, a few reports demonstrated that MEK5 protein was overexpressed and associated with certain types of cancer (12,13), for example, cancers of breast, lung, colorectal, prostate and leukemia and neuroblastoma (14)(15)(16)(17)(18)(19)(20)(21)(22). Besides, MEK5/Erk5 signal pathway has been reported to regulate angiogenesis and tumor cell proliferation (12,23). Notably, MEK5 has also been observed to play a role in EMT during breast cancer progression and metastasis by proteomics analysis (16,24,25).…”

Section: Introductionmentioning

confidence: 99%

Upregulation of MEK5 by Stat3 promotes breast cancer cell invasion and metastasis

2016

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Mitogen extracellular-signal-regulated kinase kinase 5 (MEK5) plays an important role in promoting cell proliferation and tumorigenesis. The aberrant expression of MEK5 has been reported in various malignant diseases including cancers of breast, prostate, lung, colorectal and brain. However, the function and regulation of MEK5 signaling pathway are ambiguous and remain elusive with respect to its oncogenic roles in various cancers, especially in the regulation of the initiation and progression of cancer invasion and metastasis. Ectopic expression of MEK5 or knockdown of MEK5 by shRNA with in vitro cell based models demonstrated the role of MEK5 in regulation of epithelial mesenchymal transition (EMT) and breast cancer invasion and metastasis. Here, we show that MEK5 upregulated by Stat3 promotes breast cancer cell invasion through EMT. Further study demonstrated that Stat3 could bind to promoter region of MEK5 and enhanced MEK5 transcription and expression. In addition, the phosphorylation of MEK5 significantly increased in breast cancer cells corresponding to metastatic capability of breast cancer cells. The depletion of MEK5 by shRNA significantly decreased breast cancer invasion. Ectopic expression of MEK5 could confer non-invasive breast cancer cells to become invasion capable cells. Moreover, the phosphorylation of Erk5, a MEK5-regulated downstream kinase, was also upregulated consistent with the increased level of active MEK5. Our studies provide insights into a molecular mechanism by which MEK5 transcriptionally upregulated by Stat3 augments breast cancer cell EMT, which subsequently enhances cancer cell invasion and metastasis. This finding may suggest that Stat3 and MEK5/Erk5 pathways could be an effective therapeutic target for inhibition of breast cancer invasion and metastasis.

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Can tumor cells proliferate without ERK5?

Cited by 5 publications

References 7 publications

Clinical Significance and Regulation of ERK5 Expression and Function in Cancer

Clinical Significance and Regulation of ERK5 Expression and Function in Cancer

Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer

Upregulation of MEK5 by Stat3 promotes breast cancer cell invasion and metastasis

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