Unconventional Protein Secretion in Brain Tumors Biology: Enlightening the Mechanisms for Tumor Survival and Progression

Iglesia, Rebeca Piatniczka; Prado, Mariana Brandão; Alves, Rodrigo Nunes; Escobar, Maria Isabel Melo; Fernandes, Camila Felix de Lima; Fortes, Ailine Cibele dos Santos; Souza, Maria Clara da Silva; Boccacino, Jacqueline Marcia; Cangiano, Giovanni; Soares, Samuel Ribeiro; Araújo, João Pedro Alves de; Tiek, Deanna; Goenka, Anshika; Song, Xian‐Rong; Keady, Jack Ryan; Hu, Bo; Cheng, Shi Yuan; Lopes, Marilene H.

doi:10.3389/fcell.2022.907423

Cited by 6 publications

(3 citation statements)

References 249 publications

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“…From this point of view, saliva could represent a useful biofluid to deeply investigate the rate of protein citrullination in adult and pediatric brain tumors and to discover potential biomarkers of diagnosis and early recurrence. This perspective is supported by a recent review paper that interestingly outlines the role of conventional and unconventional secreted proteins/peptides in brain tumor cell communications and microenvironments, and in tumor survival and progression [ 63 ], considering that secreted proteins include several substrates of PAD enzymes. A recent paper outlined a role of protein citrullination in the Warburg effect, which occurs in cancer cells, hyper-stimulating the glycolysis process through the regulation of PKM2 by deimination [ 64 ], which should also be investigated in brain tumors, since, to the best of our knowledge, it has not yet been studied.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Citrullination Post-Translational Modification: State of the Art of Brain Tumor Investigations and Future Perspectives

Rossetti,

Muntiu,

Massimi

et al. 2023

Diagnostics

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The present review aims to describe the state of the art of research studies investigating the citrullination post-translational modification in adult and pediatric brain tumors. After an introduction to the deimination reaction and its occurrence in proteins and polypeptide chains, the role of the citrullination post-translational modification in physiological as well as pathological states, including cancer, is summarized, and the recent literature and review papers on the topic are examined. A separate section deals with the specific focus of investigation of the citrullination post-translational modification in relation to brain tumors, examining the state of the art of the literature that mainly concerns adult and pediatric glioblastoma and posterior fossa pediatric tumors. We examined the literature on this emerging field of research, and we apologize in advance for any possible omission. Although only a few studies inspecting citrullination in brain tumors are currently available, the results interestingly highlighted different profiles of the citrullinome associated with different histotypes. The data outlined the importance of this post-translational modification in modulating cancer invasion and chemoresistance, influencing key factors involved in apoptosis, cancer cell communication through extracellular vesicle release, autophagy, and gene expression processes, which suggests the prospect of taking citrullination as a target of cancer treatment or as a source of potential diagnostic and prognostic biomarkers for potential clinical applications in the future.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Citrullination Post-Translational Modification: State of the Art of Brain Tumor Investigations and Future Perspectives

Rossetti,

Muntiu,

Massimi

et al. 2023

Diagnostics

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“…Brain tumors, such as aggressive gliomas and fatal cancers with dismal prognosis, include various UPS proteins involved in growth, proliferation and invasion. In other words, UPS machinery participates in the aggression and maintenance of brain tumors [ 34 ].…”

Section: Role Of Ups In Diseasesmentioning

confidence: 99%

Unconventional protein secretion (UPS): role in important diseases

Meldolesi

2023

Mol Biomed

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Unconventional protein secretion (UPS) is the new secretion process discovered in liquid form over three decades ago. More recently, UPS has been shown to operate also in solid forms generated from four types of organelles: fractions of lysosomes and autophagy (APh) undergoing exocytosis; exosomes and ectosomes, with their extracellular vesicles (EVs). Recently many mechanisms and proteins of these solid forms have been shown to depend on UPS. An additional function of UPS is the regulation of diseases, often investigated separately from each other. In the present review, upon short presentation of UPS in healthy cells and organs, interest is focused on the mechanisms and development of diseases. The first reported are neurodegenerations, characterized by distinct properties. Additional diseases, including inflammasomes, inflammatory responses, glial effects and other diseases of various origin, are governed by proteins generated, directly or alternatively, by UPS. The diseases most intensely affected by UPS are various types of cancer, activated in most important processes: growth, proliferation and invasion, relapse, metastatic colonization, vascular leakiness, immunomodulation, chemoresistence. The therapy role of UPS diseases depends largely on exosomes. In addition to affecting neurodegenerative diseases, its special aim is the increased protection against cancer. Its immense relevance is due to intrinsic features, including low immunogenicity, biocompatibility, stability, and crossing of biological barriers. Exosomes, loaded with factors for pharmacological actions and target cell sensitivity, induce protection against various specific cancers. Further expansion of disease therapies is expected in the near future.

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“…Diffusible factors secreted by GBM adversely affect NSCs via induction of oxidative stress [ 18 ]. GBM also uses non-canonical pathways for unconventional protein secretion to maintain the tumor [ 19 ]. On the other hand, NSCs secrete immune-modulatory factors with a regenerative effect, along with chemokines, cytokines, and proteins involved in cell signaling pathways [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Coculture with Neural Stem Cells May Shift the Transcription Profile of Glioblastoma Multiforme towards Cancer-Specific Stemness

Vaidya

Sreerama

Gonzalez-Vega

et al. 2023

IJMS

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Glioblastoma multiforme (GBM) possesses a small but significant population of cancer stem cells (CSCs) thought to play a role in its invasiveness, recurrence, and metastasis. The CSCs display transcriptional profiles for multipotency, self-renewal, tumorigenesis, and therapy resistance. There are two possible theories regarding the origin of CSCs in the context of neural stem cells (NSCs); i.e., NSCs modify cancer cells by conferring them with cancer-specific stemness, or NSCs themselves are transformed into CSCs due to the tumor environment created by cancer cells. To test the theories and to investigate the transcriptional regulation of the genes involved in CSC formation, we cocultured NSC and GBM cell lines together. Where genes related to cancer stemness, drug efflux, and DNA modification were upregulated in GBM, they were downregulated in NSCs upon coculture. These results indicate that cancer cells shift the transcriptional profile towards stemness and drug resistance in the presence of NSCs. Concurrently, GBM triggers NSCs differentiation. Because the cell lines were separated by a membrane (0.4 µm pore size) to prevent direct contact between GBM and NSCs, cell-secreted signaling molecules and extracellular vesicles (EVs) are likely involved in reciprocal communication between NSCs and GBM, causing transcription modification. Understanding the mechanism of CSC creation will aid in the identification of precise molecular targets within the CSCs to exterminate them, which, in turn, will increase the efficacy of chemo-radiation treatment.

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Unconventional Protein Secretion in Brain Tumors Biology: Enlightening the Mechanisms for Tumor Survival and Progression

Cited by 6 publications

References 249 publications

Citrullination Post-Translational Modification: State of the Art of Brain Tumor Investigations and Future Perspectives

Citrullination Post-Translational Modification: State of the Art of Brain Tumor Investigations and Future Perspectives

Unconventional protein secretion (UPS): role in important diseases

Coculture with Neural Stem Cells May Shift the Transcription Profile of Glioblastoma Multiforme towards Cancer-Specific Stemness

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