Targeting COPZ1 non-oncogene addiction counteracts the viability of thyroid tumor cells

Anania, Maria Chiara; Cetti, Elena; Lecis, Daniele; Todoerti, Katia; Gulino, Alessandro; Mauro, Giuseppe; Marco, Tiziana Di; Cleris, Loredana; Pagliardini, Sonia; Manenti, Giacomo; Belmonte, Beatrice; Tripodo, Claudio; Neri, Antonino; Greco, Angela

doi:10.1016/j.canlet.2017.09.024

Cited by 19 publications

(24 citation statements)

References 44 publications

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“…A single series of 407 unique cases was obtained, thus comprising 176 PTC, 52 ATC, 22 PDTC, and 4 FTC, together with 153 normal thyroid samples. Robust Multi-array Average (RMA) normalization [46], BrainArray annotation (http://brainarray.mbni.med.umich.edu/, version 20.0.0) [47] and batch correction by sva R/Bioconductor package [48] were applied to raw intensity values, as previously described [49].…”

Section: Gene Expression Profiles-public Datasetsmentioning

confidence: 99%

Cancer Associated Fibroblasts and Senescent Thyroid Cells in the Invasive Front of Thyroid Carcinoma

Minna

Brich

Todoerti

et al. 2020

Cancers

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Thyroid carcinoma (TC) comprises several histotypes with different aggressiveness, from well (papillary carcinoma, PTC) to less differentiated forms (poorly differentiated and anaplastic thyroid carcinoma, PDTC and ATC, respectively). Previous reports have suggested a functional role for cancer-associated fibroblasts (CAFs) or senescent TC cells in the progression of PTC. In this study, we investigated the presence of CAFs and senescent cells in proprietary human TCs including PTC, PDTC, and ATC. Screening for the driving lesions BRAFV600E and N/H/KRAS mutations, and gene fusions was also performed to correlate results with tumor genotype. In samples with unidentified drivers, transcriptomic profiles were used to establish a BRAF- or RAS-like molecular subtype based on a gene signature derived from The Cancer Genome Atlas. By using immunohistochemistry, we found co-occurrence of stromal CAFs and senescent TC cells at the tumor invasive front, where deposition of collagen (COL1A1) and expression of lysyl oxidase (LOX) enzyme were also detected, in association with features of local invasion. Concurrent high expression of CAFs and of the senescent TC cells markers, COL1A1 and LOX was confirmed in different TC histotypes in proprietary and public gene sets derived from Gene Expression Omnibus (GEO) repository, and especially in BRAF mutated or BRAF-like tumors. In this study, we show that CAFs and senescent TC cells co-occur in various histotypes of BRAF-driven thyroid tumors and localize at the tumor invasive front.

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Section: Gene Expression Profiles-public Datasetsmentioning

confidence: 99%

Cancer Associated Fibroblasts and Senescent Thyroid Cells in the Invasive Front of Thyroid Carcinoma

Minna

Brich

Todoerti

et al. 2020

Cancers

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“…Interestingly, the same authors found that COPZ1 vulnerability of tumor cells relies on the downregulation of the isoform COPZ2, whose gene hosts the well-known oncosuppressor miRNA152 [115,116]. We found that COPZ1 represents vulnerability for TC, as it is required for the viability of different TC cell lines but not of normal thyrocytes [117]. Moreover, the absence of mutation and aberrant expression in PTC [76] renders COPZ1 a good example of NOA for thyroid cancer cells.…”

Section: Validation Of Noa Targetsmentioning

confidence: 61%

Targeting Non-Oncogene Addiction: Focus on Thyroid Cancer

Anania

Marco

Mazzoni

et al. 2020

Cancers

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Thyroid carcinoma (TC) is the most common malignancy of endocrine organs with an increasing incidence in industrialized countries. The majority of TC are characterized by a good prognosis, even though cases with aggressive forms not cured by standard therapies are also present. Moreover, target therapies have led to low rates of partial response and prompted the emergence of resistance, indicating that new therapies are needed. In this review, we summarize current literature about the non-oncogene addiction (NOA) concept, which indicates that cancer cells, at variance with normal cells, rely on the activity of genes, usually not mutated or aberrantly expressed, essential for coping with the transformed phenotype. We highlight the potential of non-oncogenes as a point of intervention for cancer therapy in general, and present evidence for new putative non-oncogenes that are essential for TC survival and that may constitute attractive new therapeutic targets.

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“…We reveal here a role for g1-COP in promoting neurite outgrowth, and it is likely that in other cellular contexts additional paralog-specific functions of COP subunits await to be found. Of note, many cancer cell lines are sensitive to a down-regulation of z1-COP because they barely express its paralog z2-COP 43,54,55 .…”

Section: Discussionmentioning

confidence: 99%

“…Potential drugs that would target z1-COP have thus been proposed as attractive therapeutic options with supposedly limited side effects because z2-COP is expressed in normal cells 55,56 . Our study calls for caution when following such approaches as z1-COP, like g1-COP, may have important functions that cannot be taken over by its paralog in specific cellular contexts.…”

Section: Discussionmentioning

confidence: 99%

A paralog-specific role of the COPI pathway in the neuronal differentiation of murine pluripotent cells

Goyal

Zhao

Bozhinova

et al. 2020

Preprint

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Coat protein complex I (COPI)-coated vesicles mediate membrane trafficking between Golgi cisternae as well as retrieval of proteins from the Golgi to the endoplasmic reticulum. There are several flavors of the COPI coat defined by paralogous subunits of the protein complex coatomer. However, whether paralogous COPI proteins have specific functions is currently unknown. Here we show that the paralogous coatomer subunits g1-COP and g2-COP are differentially expressed during the neuronal differentiation of mouse pluripotent cells. Moreover, through a combination of genome editing experiments, we demonstrate that whereas g-COP paralogs are largely functionally redundant, g1-COP specifically promotes neurite outgrowth. Our work stresses a role of the COPI pathway in neuronal polarization and provides evidence for distinct functions for coatomer paralogous subunits in this process.

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Targeting COPZ1 non-oncogene addiction counteracts the viability of thyroid tumor cells

Cited by 19 publications

References 44 publications

Cancer Associated Fibroblasts and Senescent Thyroid Cells in the Invasive Front of Thyroid Carcinoma

Cancer Associated Fibroblasts and Senescent Thyroid Cells in the Invasive Front of Thyroid Carcinoma

Targeting Non-Oncogene Addiction: Focus on Thyroid Cancer

A paralog-specific role of the COPI pathway in the neuronal differentiation of murine pluripotent cells

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