--- _id: '12268' abstract: - lang: eng text: The complexity of the microenvironment effects on cell response, show accumulating evidence that glioblastoma (GBM) migration and invasiveness are influenced by the mechanical rigidity of their surroundings. The epithelial–mesenchymal transition (EMT) is a well-recognized driving force of the invasive behavior of cancer. However, the primary mechanisms of EMT initiation and progression remain unclear. We have previously showed that certain substrate stiffness can selectively stimulate human GBM U251-MG and GL15 glioblastoma cell lines motility. The present study unifies several known EMT mediators to uncover the reason of the regulation and response to these stiffnesses. Our results revealed that changing the rigidity of the mechanical environment tuned the response of both cell lines through change in morphological features, epithelial-mesenchymal markers (E-, N-Cadherin), EGFR and ROS expressions in an interrelated manner. Specifically, a stiffer microenvironment induced a mesenchymal cell shape, a more fragmented morphology, higher intracellular cytosolic ROS expression and lower mitochondrial ROS. Finally, we observed that cells more motile showed a more depolarized mitochondrial membrane potential. Unravelling the process that regulates GBM cells’ infiltrative behavior could provide new opportunities for identification of new targets and less invasive approaches for treatment. acknowledgement: "The research leading to these results has received funding from AIRC under IG 2021 - ID. 26328 project – P.I. Cortese Barbara and AIRC under MFAG 2015 - ID. 16803 project – “P.I. Cortese Barbara”. The authors are also grateful to the ”Tecnopolo per la medicina di precisione” (TecnoMed Puglia) - Regione Puglia: DGR n.2117 del 21/11/2018, CUP: B84I18000540002 and “Tecnopolo di Nanotecnologia e Fotonica per la medicina di precisione” (TECNOMED) - FISR/MIUR-CNR: delibera CIPE n.3449 del 7-08-2017, CUP: B83B17000010001.\r\nWe thank Dr. Francesca Pagani for useful technical support. We thank also Irene Iacuitto, Giovanna Loffredo and Manuela Marchetti for practical administrative support." article_number: '983507' article_processing_charge: No article_type: original author: - first_name: Bernadette full_name: Basilico, Bernadette id: 36035796-5ACA-11E9-A75E-7AF2E5697425 last_name: Basilico orcid: 0000-0003-1843-3173 - first_name: Ilaria Elena full_name: Palamà, Ilaria Elena last_name: Palamà - first_name: Stefania full_name: D’Amone, Stefania last_name: D’Amone - first_name: Clotilde full_name: Lauro, Clotilde last_name: Lauro - first_name: Maria full_name: Rosito, Maria last_name: Rosito - first_name: Maddalena full_name: Grieco, Maddalena last_name: Grieco - first_name: Patrizia full_name: Ratano, Patrizia last_name: Ratano - first_name: Federica full_name: Cordella, Federica last_name: Cordella - first_name: Caterina full_name: Sanchini, Caterina last_name: Sanchini - first_name: Silvia full_name: Di Angelantonio, Silvia last_name: Di Angelantonio - first_name: Davide full_name: Ragozzino, Davide last_name: Ragozzino - first_name: Mariafrancesca full_name: Cascione, Mariafrancesca last_name: Cascione - first_name: Giuseppe full_name: Gigli, Giuseppe last_name: Gigli - first_name: Barbara full_name: Cortese, Barbara last_name: Cortese citation: ama: Basilico B, Palamà IE, D’Amone S, et al. Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. Frontiers in Oncology. 2022;12. doi:10.3389/fonc.2022.983507 apa: Basilico, B., Palamà, I. E., D’Amone, S., Lauro, C., Rosito, M., Grieco, M., … Cortese, B. (2022). Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. Frontiers in Oncology. Frontiers Media. https://doi.org/10.3389/fonc.2022.983507 chicago: Basilico, Bernadette, Ilaria Elena Palamà, Stefania D’Amone, Clotilde Lauro, Maria Rosito, Maddalena Grieco, Patrizia Ratano, et al. “Substrate Stiffness Effect on Molecular Crosstalk of Epithelial-Mesenchymal Transition Mediators of Human Glioblastoma Cells.” Frontiers in Oncology. Frontiers Media, 2022. https://doi.org/10.3389/fonc.2022.983507. ieee: B. Basilico et al., “Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells,” Frontiers in Oncology, vol. 12. Frontiers Media, 2022. ista: Basilico B, Palamà IE, D’Amone S, Lauro C, Rosito M, Grieco M, Ratano P, Cordella F, Sanchini C, Di Angelantonio S, Ragozzino D, Cascione M, Gigli G, Cortese B. 2022. Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. Frontiers in Oncology. 12, 983507. mla: Basilico, Bernadette, et al. “Substrate Stiffness Effect on Molecular Crosstalk of Epithelial-Mesenchymal Transition Mediators of Human Glioblastoma Cells.” Frontiers in Oncology, vol. 12, 983507, Frontiers Media, 2022, doi:10.3389/fonc.2022.983507. short: B. Basilico, I.E. Palamà, S. D’Amone, C. Lauro, M. Rosito, M. Grieco, P. Ratano, F. Cordella, C. Sanchini, S. Di Angelantonio, D. Ragozzino, M. Cascione, G. Gigli, B. Cortese, Frontiers in Oncology 12 (2022). date_created: 2023-01-16T10:00:28Z date_published: 2022-08-25T00:00:00Z date_updated: 2023-08-04T09:54:16Z day: '25' ddc: - '570' department: - _id: GaNo doi: 10.3389/fonc.2022.983507 external_id: isi: - '000856524900001' pmid: - '36091138' file: - access_level: open_access checksum: efc7edf9f626af31853790c5b598a68c content_type: application/pdf creator: dernst date_created: 2023-01-30T10:25:21Z date_updated: 2023-01-30T10:25:21Z file_id: '12450' file_name: 2022_FrontiersOntology_Basilico.pdf file_size: 13588502 relation: main_file success: 1 file_date_updated: 2023-01-30T10:25:21Z has_accepted_license: '1' intvolume: ' 12' isi: 1 keyword: - Cancer Research - Oncology language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '08' oa: 1 oa_version: Published Version pmid: 1 publication: Frontiers in Oncology publication_identifier: issn: - 2234-943X publication_status: published publisher: Frontiers Media quality_controlled: '1' scopus_import: '1' status: public title: Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 12 year: '2022' ... --- _id: '15272' abstract: - lang: eng text: The assembly of neuronal circuits involves the migrations of neurons from their place of birth to their final location in the nervous system, as well as the coordinated growth and patterning of axons and dendrites. In screens for genes required for patterning of the nervous system, we identified the catp-8/P5A-ATPase as an important regulator of neural patterning. P5A-ATPases are part of the P-type ATPases, a family of proteins known to serve a conserved function as transporters of ions, lipids and polyamines in unicellular eukaryotes, plants, and humans. While the function of many P-type ATPases is relatively well understood, the function of P5A-ATPases in metazoans remained elusive. We show here, that the Caenorhabditis elegans ortholog catp-8/P5A-ATPase is required for defined aspects of nervous system development. Specifically, the catp-8/P5A-ATPase serves functions in shaping the elaborately sculpted dendritic trees of somatosensory PVD neurons. Moreover, catp-8/P5A-ATPase is required for axonal guidance and repulsion at the midline, as well as embryonic and postembryonic neuronal migrations. Interestingly, not all axons at the midline require catp-8/P5A-ATPase, although the axons run in the same fascicles and navigate the same space. Similarly, not all neuronal migrations require catp-8/P5A-ATPase. A CATP-8/P5A-ATPase reporter is localized to the ER in most, if not all, tissues and catp-8/P5A-ATPase can function both cell-autonomously and non-autonomously to regulate neuronal development. Genetic analyses establish that catp-8/P5A-ATPase can function in multiple pathways, including the Menorin pathway, previously shown to control dendritic patterning in PVD, and Wnt signaling, which functions to control neuronal migrations. Lastly, we show that catp-8/P5A-ATPase is required for localizing select transmembrane proteins necessary for dendrite morphogenesis. Collectively, our studies suggest that catp-8/P5A-ATPase serves diverse, yet specific, roles in different genetic pathways and may be involved in the regulation or localization of transmembrane and secreted proteins to specific subcellular compartments. article_number: e1009475 article_processing_charge: No article_type: original author: - first_name: Leo T. H. full_name: Tang, Leo T. H. last_name: Tang - first_name: Meera full_name: Trivedi, Meera last_name: Trivedi - first_name: Jenna full_name: Freund, Jenna last_name: Freund - first_name: Christopher J. full_name: Salazar, Christopher J. last_name: Salazar - first_name: Maisha full_name: Rahman, Maisha last_name: Rahman - first_name: Nelson full_name: Ramirez, Nelson id: 39831956-E4FE-11E9-85DE-0DC7E5697425 last_name: Ramirez - first_name: Garrett full_name: Lee, Garrett last_name: Lee - first_name: Yu full_name: Wang, Yu last_name: Wang - first_name: Barth D. full_name: Grant, Barth D. last_name: Grant - first_name: Hannes E. full_name: Bülow, Hannes E. last_name: Bülow citation: ama: Tang LTH, Trivedi M, Freund J, et al. The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning. PLOS Genetics. 2021;17(7). doi:10.1371/journal.pgen.1009475 apa: Tang, L. T. H., Trivedi, M., Freund, J., Salazar, C. J., Rahman, M., Ramirez, N., … Bülow, H. E. (2021). The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning. PLOS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1009475 chicago: Tang, Leo T. H., Meera Trivedi, Jenna Freund, Christopher J. Salazar, Maisha Rahman, Nelson Ramirez, Garrett Lee, Yu Wang, Barth D. Grant, and Hannes E. Bülow. “The CATP-8/P5A-Type ATPase Functions in Multiple Pathways during Neuronal Patterning.” PLOS Genetics. Public Library of Science, 2021. https://doi.org/10.1371/journal.pgen.1009475. ieee: L. T. H. Tang et al., “The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning,” PLOS Genetics, vol. 17, no. 7. Public Library of Science, 2021. ista: Tang LTH, Trivedi M, Freund J, Salazar CJ, Rahman M, Ramirez N, Lee G, Wang Y, Grant BD, Bülow HE. 2021. The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning. PLOS Genetics. 17(7), e1009475. mla: Tang, Leo T. H., et al. “The CATP-8/P5A-Type ATPase Functions in Multiple Pathways during Neuronal Patterning.” PLOS Genetics, vol. 17, no. 7, e1009475, Public Library of Science, 2021, doi:10.1371/journal.pgen.1009475. short: L.T.H. Tang, M. Trivedi, J. Freund, C.J. Salazar, M. Rahman, N. Ramirez, G. Lee, Y. Wang, B.D. Grant, H.E. Bülow, PLOS Genetics 17 (2021). date_created: 2024-04-03T07:57:12Z date_published: 2021-07-01T00:00:00Z date_updated: 2024-04-10T08:57:16Z day: '01' ddc: - '570' department: - _id: MaDe doi: 10.1371/journal.pgen.1009475 external_id: pmid: - '34197450' file: - access_level: open_access checksum: 7352b195e4db6d404f702fe6ad8b55ad content_type: application/pdf creator: dernst date_created: 2024-04-10T08:53:43Z date_updated: 2024-04-10T08:53:43Z file_id: '15308' file_name: 2021_PlosGenetics_Tang.pdf file_size: 4224934 relation: main_file success: 1 file_date_updated: 2024-04-10T08:53:43Z has_accepted_license: '1' intvolume: ' 17' issue: '7' keyword: - Cancer Research - Genetics (clinical) - Genetics - Molecular Biology - Ecology - Evolution - Behavior and Systematics language: - iso: eng month: '07' oa: 1 oa_version: Published Version pmid: 1 publication: PLOS Genetics publication_identifier: issn: - 1553-7404 publication_status: published publisher: Public Library of Science quality_controlled: '1' status: public title: The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 17 year: '2021' ... --- _id: '12189' abstract: - lang: eng text: Meiotic crossovers (COs) are important for reshuffling genetic information between homologous chromosomes and they are essential for their correct segregation. COs are unevenly distributed along chromosomes and the underlying mechanisms controlling CO localization are not well understood. We previously showed that meiotic COs are mis-localized in the absence of AXR1, an enzyme involved in the neddylation/rubylation protein modification pathway in Arabidopsis thaliana. Here, we report that in axr1-/-, male meiocytes show a strong defect in chromosome pairing whereas the formation of the telomere bouquet is not affected. COs are also redistributed towards subtelomeric chromosomal ends where they frequently form clusters, in contrast to large central regions depleted in recombination. The CO suppressed regions correlate with DNA hypermethylation of transposable elements (TEs) in the CHH context in axr1-/- meiocytes. Through examining somatic methylomes, we found axr1-/- affects DNA methylation in a plant, causing hypermethylation in all sequence contexts (CG, CHG and CHH) in TEs. Impairment of the main pathways involved in DNA methylation is epistatic over axr1-/- for DNA methylation in somatic cells but does not restore regular chromosome segregation during meiosis. Collectively, our findings reveal that the neddylation pathway not only regulates hormonal perception and CO distribution but is also, directly or indirectly, a major limiting pathway of TE DNA methylation in somatic cells. acknowledgement: The authors wish to thank Cécile Raynaud, Eric Jenczewski, Rajeev Kumar, Raphaël Mercier and Jean Molinier for critical reading of the manuscript. article_number: e1008894 article_processing_charge: No article_type: original author: - first_name: Nicolas full_name: Christophorou, Nicolas last_name: Christophorou - first_name: Wenjing full_name: She, Wenjing last_name: She - first_name: Jincheng full_name: Long, Jincheng last_name: Long - first_name: Aurélie full_name: Hurel, Aurélie last_name: Hurel - first_name: Sébastien full_name: Beaubiat, Sébastien last_name: Beaubiat - first_name: Yassir full_name: Idir, Yassir last_name: Idir - first_name: Marina full_name: Tagliaro-Jahns, Marina last_name: Tagliaro-Jahns - first_name: Aurélie full_name: Chambon, Aurélie last_name: Chambon - first_name: Victor full_name: Solier, Victor last_name: Solier - first_name: Daniel full_name: Vezon, Daniel last_name: Vezon - first_name: Mathilde full_name: Grelon, Mathilde last_name: Grelon - first_name: Xiaoqi full_name: Feng, Xiaoqi id: e0164712-22ee-11ed-b12a-d80fcdf35958 last_name: Feng orcid: 0000-0002-4008-1234 - first_name: Nicolas full_name: Bouché, Nicolas last_name: Bouché - first_name: Christine full_name: Mézard, Christine last_name: Mézard citation: ama: Christophorou N, She W, Long J, et al. AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization. PLOS Genetics. 2020;16(6). doi:10.1371/journal.pgen.1008894 apa: Christophorou, N., She, W., Long, J., Hurel, A., Beaubiat, S., Idir, Y., … Mézard, C. (2020). AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization. PLOS Genetics. Public Library of Science (PLoS). https://doi.org/10.1371/journal.pgen.1008894 chicago: Christophorou, Nicolas, Wenjing She, Jincheng Long, Aurélie Hurel, Sébastien Beaubiat, Yassir Idir, Marina Tagliaro-Jahns, et al. “AXR1 Affects DNA Methylation Independently of Its Role in Regulating Meiotic Crossover Localization.” PLOS Genetics. Public Library of Science (PLoS), 2020. https://doi.org/10.1371/journal.pgen.1008894. ieee: N. Christophorou et al., “AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization,” PLOS Genetics, vol. 16, no. 6. Public Library of Science (PLoS), 2020. ista: Christophorou N, She W, Long J, Hurel A, Beaubiat S, Idir Y, Tagliaro-Jahns M, Chambon A, Solier V, Vezon D, Grelon M, Feng X, Bouché N, Mézard C. 2020. AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization. PLOS Genetics. 16(6), e1008894. mla: Christophorou, Nicolas, et al. “AXR1 Affects DNA Methylation Independently of Its Role in Regulating Meiotic Crossover Localization.” PLOS Genetics, vol. 16, no. 6, e1008894, Public Library of Science (PLoS), 2020, doi:10.1371/journal.pgen.1008894. short: N. Christophorou, W. She, J. Long, A. Hurel, S. Beaubiat, Y. Idir, M. Tagliaro-Jahns, A. Chambon, V. Solier, D. Vezon, M. Grelon, X. Feng, N. Bouché, C. Mézard, PLOS Genetics 16 (2020). date_created: 2023-01-16T09:16:10Z date_published: 2020-06-29T00:00:00Z date_updated: 2023-05-08T10:54:39Z day: '29' department: - _id: XiFe doi: 10.1371/journal.pgen.1008894 extern: '1' external_id: pmid: - '32598340' intvolume: ' 16' issue: '6' keyword: - Cancer Research - Genetics (clinical) - Genetics - Molecular Biology - Ecology - Evolution - Behavior and Systematics language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351236/ month: '06' oa: 1 oa_version: Published Version pmid: 1 publication: PLOS Genetics publication_identifier: issn: - 1553-7404 publication_status: published publisher: Public Library of Science (PLoS) quality_controlled: '1' scopus_import: '1' status: public title: AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 16 year: '2020' ... --- _id: '11086' abstract: - lang: eng text: Faithful execution of developmental gene expression programs occurs at multiple levels and involves many different components such as transcription factors, histone-modification enzymes, and mRNA processing proteins. Recent evidence suggests that nucleoporins, well known components that control nucleo-cytoplasmic trafficking, have wide-ranging functions in developmental gene regulation that potentially extend beyond their role in nuclear transport. Whether the unexpected role of nuclear pore proteins in transcription regulation, which initially has been described in fungi and flies, also applies to human cells is unknown. Here we show at a genome-wide level that the nuclear pore protein NUP98 associates with developmentally regulated genes active during human embryonic stem cell differentiation. Overexpression of a dominant negative fragment of NUP98 levels decreases expression levels of NUP98-bound genes. In addition, we identify two modes of developmental gene regulation by NUP98 that are differentiated by the spatial localization of NUP98 target genes. Genes in the initial stage of developmental induction can associate with NUP98 that is embedded in the nuclear pores at the nuclear periphery. Alternatively, genes that are highly induced can interact with NUP98 in the nuclear interior, away from the nuclear pores. This work demonstrates for the first time that NUP98 dynamically associates with the human genome during differentiation, revealing a role of a nuclear pore protein in regulating developmental gene expression programs. article_number: e1003308 article_processing_charge: No article_type: original author: - first_name: Yun full_name: Liang, Yun last_name: Liang - first_name: Tobias M. full_name: Franks, Tobias M. last_name: Franks - first_name: Maria C. full_name: Marchetto, Maria C. last_name: Marchetto - first_name: Fred H. full_name: Gage, Fred H. last_name: Gage - first_name: Martin W full_name: HETZER, Martin W id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed last_name: HETZER orcid: 0000-0002-2111-992X citation: ama: Liang Y, Franks TM, Marchetto MC, Gage FH, Hetzer M. Dynamic association of NUP98 with the human genome. PLoS Genetics. 2013;9(2). doi:10.1371/journal.pgen.1003308 apa: Liang, Y., Franks, T. M., Marchetto, M. C., Gage, F. H., & Hetzer, M. (2013). Dynamic association of NUP98 with the human genome. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1003308 chicago: Liang, Yun, Tobias M. Franks, Maria C. Marchetto, Fred H. Gage, and Martin Hetzer. “Dynamic Association of NUP98 with the Human Genome.” PLoS Genetics. Public Library of Science, 2013. https://doi.org/10.1371/journal.pgen.1003308. ieee: Y. Liang, T. M. Franks, M. C. Marchetto, F. H. Gage, and M. Hetzer, “Dynamic association of NUP98 with the human genome,” PLoS Genetics, vol. 9, no. 2. Public Library of Science, 2013. ista: Liang Y, Franks TM, Marchetto MC, Gage FH, Hetzer M. 2013. Dynamic association of NUP98 with the human genome. PLoS Genetics. 9(2), e1003308. mla: Liang, Yun, et al. “Dynamic Association of NUP98 with the Human Genome.” PLoS Genetics, vol. 9, no. 2, e1003308, Public Library of Science, 2013, doi:10.1371/journal.pgen.1003308. short: Y. Liang, T.M. Franks, M.C. Marchetto, F.H. Gage, M. Hetzer, PLoS Genetics 9 (2013). date_created: 2022-04-07T07:50:59Z date_published: 2013-02-28T00:00:00Z date_updated: 2024-10-14T11:24:40Z day: '28' doi: 10.1371/journal.pgen.1003308 extern: '1' external_id: pmid: - '23468646' intvolume: ' 9' issue: '2' keyword: - Cancer Research - Genetics (clinical) - Genetics - Molecular Biology - Ecology - Evolution - Behavior and Systematics language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1371/journal.pgen.1003308 month: '02' oa: 1 oa_version: Published Version pmid: 1 publication: PLoS Genetics publication_identifier: issn: - 1553-7404 publication_status: published publisher: Public Library of Science quality_controlled: '1' scopus_import: '1' status: public title: Dynamic association of NUP98 with the human genome type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 9 year: '2013' ...