The double face of Morgana in tumorigenesis

Brancaccio, Mara; Rocca, Stefania; Seclì, Laura; Busso, Elena; Fusella, Federica

doi:10.18632/oncotarget.6058

Cited by 10 publications

(7 citation statements)

References 78 publications

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“…Especially, reduced ESRP1 expression switches FGFR2 expression to more mesenchymal splice variants with a strong potential of disease progression, and showed a correlation between ESRPs expression and a favorable outcome in CRC. These are not surprising considering the evidences showing that a number of genes, often coding for multifunctional proteins like ESRP1, show oncogenic activities both when over- or under-expressed, highlighting a need for fine tuning of their expression levels in normal cells [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

The RNA-binding protein ESRP1 promotes human colorectal cancer progression

et al. 2016

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Epithelial splicing regulatory protein 1 (ESRP1) is an epithelial cell-specific RNA binding protein that controls several key cellular processes, like alternative splicing and translation. Previous studies have demonstrated a tumor suppressor role for this protein. Recently, however, a pro-metastatic function of ESRP1 has been reported. We thus aimed at clarifying the role of ESRP1 in Colorectal Cancer (CRC) by performing loss- and gain-of-function studies, and evaluating tumorigenesis and malignancy with in vitro and in vivo approaches. We found that ESRP1 plays a role in anchorage-independent growth of CRC cells. ESRP1-overexpressing cells grown in suspension showed enhanced fibroblast growth factor receptor (FGFR1/2) signalling, Akt activation, and Snail upregulation. Moreover, ESRP1 promoted the ability of CRC cells to generate macrometastases in mice livers. High ESRP1 expression may thus stimulate growth of cancer epithelial cells and promote colorectal cancer progression. Our findings provide mechanistic insights into a previously unreported, pro-oncogenic role for ESRP1 in CRC, and suggest that fine-tuning the level of this RNA-binding protein could be relevant in modulating tumor growth in a subset of CRC patients.

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Section: Discussionmentioning

confidence: 99%

The RNA-binding protein ESRP1 promotes human colorectal cancer progression

et al. 2016

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“…Morgana, also known as CHP-1, is a small chaperone ubiquitously expressed coded by the CHORDC1 gene [85][86][87][88].…”

Section: Morganamentioning

confidence: 99%

The one thousand and one chaperones of the NF-κB pathway

Fusella

Seclì

Cannata

et al. 2019

Cell. Mol. Life Sci.

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The NF-B pathway represents a crucial signaling mechanism in sensing and integrating a multitude of environmental and intracellular stimuli and directing a coordinated response that from the cellular level may impact on the entire organism. A plethora of chaperone proteins works at multiple steps of the pathway, from membrane receptor activation to transcription factor binding to DNA. Indeed, chaperones are required to assist protein conformational changes, to assemble supramolecular complexes and to regulate protein ubiquitination, required for pathway activation. Some chaperones acquired a role as integral components of the signaling complexes, needed for signal progression. Here we describe the chaperones involved in the NF-B pathway and their specific roles in the different contexts.

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“…Morgana binds to Hsp90 chaperone protein 17 – 22 , behaving as a co-chaperone 17 and interacts with and inhibits Rho kinases I and II 14 , 20 , 23 . Morgana displays oncogenic features, conferring resistance to apoptosis when overexpressed 24 . Indeed, high Morgana expression levels by excessively inhibiting ROCK I activity, destabilize PTEN, hence triggering the PI3K/AKT survival pathway 14 .…”

Section: Introductionmentioning

confidence: 99%

The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis

et al. 2017

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NF-κB is a transcription factor involved in the regulation of multiple physiological and pathological cellular processes, including inflammation, cell survival, proliferation, and cancer cell metastasis. NF-κB is frequently hyperactivated in several cancers, including triple-negative breast cancer. Here we show that NF-κB activation in breast cancer cells depends on the presence of the CHORDC1 gene product Morgana, a previously unknown component of the IKK complex and essential for IκBα substrate recognition. Morgana silencing blocks metastasis formation in breast cancer mouse models and this phenotype is reverted by IκBα downregulation. High Morgana expression levels in cancer cells decrease recruitment of natural killer cells in the first phases of tumor growth and induce the expression of cytokines able to attract neutrophils in the primary tumor, as well as in the pre-metastatic lungs, fueling cancer metastasis. In accordance, high Morgana levels positively correlate with NF-κB target gene expression and poor prognosis in human patients.

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The double face of Morgana in tumorigenesis

Cited by 10 publications

References 78 publications

The RNA-binding protein ESRP1 promotes human colorectal cancer progression

The RNA-binding protein ESRP1 promotes human colorectal cancer progression

The one thousand and one chaperones of the NF-κB pathway

The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis

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