Role of the Non-Receptor Tyrosine Kinase Fes in Cancer

Condorelli, Fabrizio; Stec-Martyna, E.; Zaborowska, J.; Felli, Lamberto; Gnemmi, Ilaria; Ponassi, Marco; Rosano, Camillo

doi:10.2174/092986711796150522

Cited by 12 publications

(8 citation statements)

References 90 publications

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“…For instance, mutations in ezrin within the conserved threonine residue prevent the formation of E-cadherinmediated cel-cell contacts during blastocyst formation in mice (Dard et al, 2001). It has been suggested that the small pool of ezrin that is present at cell-cell contacts is sufficient to recruit Fes kinase -a non-RTK that has also been implicated in cancer progression (Condorelli et al, 2011) -and to modulate junction formation by directly interacting with the SH2 domain of Fes kinase (Naba et al, 2008). This interaction is important for the localisation and activation of Fes, which consequently results in the disassembly of cell-cell contacts.…”

Section: Ezrinmentioning

confidence: 99%

“…Furthermore, knockdown of radixin in PANC-1 cells resulted in an increase in E-cadherin expression, which is also seen in ezrindepleted cells . This implies that both ezrin and radixin may have an important role in the disruption of cell-cell contacts through the downregulation of E-cadherin and its relocalisation during cancer progression Condorelli et al, 2011;Li et al, 2012;Pujuguet et al, 2003).…”

Section: Radixinmentioning

confidence: 99%

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ERM proteins in cancer progression

Clucas

Valderrama

2014

Journal of Cell Science

223

152

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Members of the ezrin–radixin–moesin (ERM) family of proteins are involved in multiple aspects of cell migration by acting both as crosslinkers between the membrane, receptors and the actin cytoskeleton, and as regulators of signalling molecules that are implicated in cell adhesion, cell polarity and migration. Increasing evidence suggests that the regulation of cell signalling and the cytoskeleton by ERM proteins is crucial during cancer progression. Thus, both their expression levels and subcellular localisation would affect tumour progression. High expression of ERM proteins has been shown in a variety of cancers. Mislocalisation of ERM proteins reduces the ability of cells to form cell–cell contacts and, therefore, promotes an invasive phenotype. Similarly, mislocalisation of ERM proteins impairs the formation of receptor complexes and alters the transmission of signals in response to growth factors, thereby facilitating tumour progression. In this Commentary, we address the structure, function and regulation of ERM proteins under normal physiological conditions as well as in cancer progression, with particular emphasis on cancers of epithelial origin, such as those from breast, lung and prostate. We also discuss any recent developments that have added to the understanding of the underlying molecular mechanisms and signalling pathways these proteins are involved in during cancer progression.

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Section: Ezrinmentioning

confidence: 99%

Section: Radixinmentioning

confidence: 99%

ERM proteins in cancer progression

Clucas

Valderrama

2014

Journal of Cell Science

223

152

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“…PJA2 encodes an E3 ubiquitin‐protein ligase, and although the precise function of PJA2 has not been clarified, its expression level is moderately high in almost all normal tissues according to our present quantitative RT‐PCR results and microarray analysis (RefExA, http://www.lsbm.org/). FER is a 94‐kDa non‐receptor tyrosine kinase involved in the reorganization of the actin cytoskeleton or the modulation of cell–cell and cell–substrate interactions through its association with adhesion molecules and has been reported to play a role in the proliferation and growth of several cancers, such as prostate cancer, colon cancer, breast cancer, hepatocellular carcinoma, malignant mesothelioma, and gastric cancer . Especially, very recently, FER expression has been shown to be correlated with poor prognosis in NSCLC and renal cell carcinoma …”

Section: Discussionmentioning

confidence: 99%

Detection of novel paraja ring finger 2‐fer tyrosine kinase mRNA chimeras is associated with poor postoperative prognosis in non‐small cell lung cancer

et al. 2013

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Previously, we reported that the overexpression of fer tyrosine kinase (FER), a non‐receptor tyrosine kinase, is correlated with poor postoperative prognosis and cancer‐cell survival in non‐small cell lung cancer (NSCLC). In the present study, we further analyzed FER‐overexpressed NSCLC cases and identified various patterns of chimeric mRNAs, composed of paraja ring finger 2 (PJA2) and FER. We detected no genomic rearrangements between PJA2 and FER and attributed these chimeric mRNAs to alterations at the transcriptome level: i.e., trans‐splicing. Several chimeric patterns were detected concurrently in each patient, and the pattern sets varied among patients, although the pattern in which PJA2 exon 1 was fused to FER exon 3 (designated as Pe1‐Fe3 mRNA) was detected constantly. Therefore, in a wide screening for PJA2‐FER mRNAs in NSCLC, we focused on this chimeric pattern as a representative chimera. In analyses of 167 NSCLC samples, Pe1‐Fe3 mRNA was identified in about 10% of the patients, and the presence of chimeric mRNA was significantly correlated with a high expression level of parental FER mRNA. Furthermore, we found that the detection of Pe1‐Fe3 mRNA was correlated with poor postoperative survival periods in NSCLC, consistent with a previous finding in which FER overexpression was correlated with poor postoperative prognosis in NSCLC. This report is the first to suggest a correlation between chimeric mRNA and the expression level of parental mRNA. Furthermore, our findings may be clinically beneficial, suggesting that PJA2‐FER mRNAs might serve as a novel prognostic biomarker in NSCLC.

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“…Activation of FES kinase requires active phosphorylation of Tyr713 located inside the activation loop and of Tyr 811. Hyperactivation of FES kinase is necessary for deregulated proliferation in human lymphoid malignancies, but aberrant activation is not associated with human tumors [17].…”

Section: Feline Sarcoma (Fes) Kinasesmentioning

confidence: 99%

Non-receptor Tyrosine Kinases Role and Significance in Hematological Malignancies

Azevedo¹,

Silva²,

Rueff³

2019

Tyrosine Kinases as Druggable Targets in Cancer

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This chapter presents a review about non-receptor tyrosine kinases, their structure, mechanisms of action and physiopathology, and how they are regulated and interact with other molecules and other signaling pathways, contributing to the regulation of fundamental cellular functions such as cell division and differentiation, stress responses, apoptosis, survival, and proliferation, gene expression, immune response, inter alia. Special emphasis will be assigned to the JAK family, the processes whereby it can be mutated/regulated and aberrantly activated, clinical significance and association with hematological disease progression and malignancy, mainly in myeloproliferative neoplasms. Consideration of these mechanisms may have important implications for selection of anti-cancer targeted therapies.

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Role of the Non-Receptor Tyrosine Kinase Fes in Cancer

Cited by 12 publications

References 90 publications

ERM proteins in cancer progression

ERM proteins in cancer progression

Detection of novel paraja ring finger 2‐fer tyrosine kinase mRNA chimeras is associated with poor postoperative prognosis in non‐small cell lung cancer

Non-receptor Tyrosine Kinases Role and Significance in Hematological Malignancies

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