Molecular Profiling of Low‐Grade Appendiceal Mucinous Neoplasms (LAMN) DOI Creative Commons
Julia Doll, Katja Maurus,

Franziska Köhler

и другие.

Genes Chromosomes and Cancer, Год журнала: 2024, Номер 63(10)

Опубликована: Окт. 1, 2024

ABSTRACT Low‐grade appendiceal mucinous neoplasia (LAMN) represents a relatively rare tumor of the appendix typically diagnosed incidentally through appendectomy for acute appendicitis. In cases where perforation occurs, content may disseminate into abdominal cavity, leading to development pseudomyxoma peritonei (PMP). The primary objective this study was elucidate molecular characteristics associated with various stages LAMN and PMP. DNA extracted from LAMN, PMPs, recurrent adenocarcinomas originating LAMN. subsequent analysis involved examination mutational hotspot regions within 50 cancer‐related genes, covering over 2800 COSMIC mutations, utilizing amplicon‐based next‐generation sequencing (NGS). Our findings revealed activating somatic mutations MAPK‐signaling pathway across all tumors examined. Specifically, 98.1% showed in KRAS , while one harbored BRAF mutation. Additionally, GNAS were identified 55.8% tumors, no significant difference observed between While rarely displayed additional 42% PMPs 60% mutations. Notably, both TP53 . Furthermore, 7.7% (4/52) exhibited potentially targetable G12C four patients, NGS performed on PMP PMP/adenocarcinoma samples. detected almost samples, 50% an SMAD4 mutation, suggesting notable alteration during disease progression. indicate two key points: First, MAPK pathway, particularly are evident along high frequency Second, progression toward or adenocarcinoma is accumulation common oncogenic pathways.

Язык: Английский

Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches DOI Creative Commons
Fangfang Liu, Jingyu Chen, Kai Li

и другие.

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Июль 25, 2024

Abstract Ubiquitination, a pivotal posttranslational modification of proteins, plays fundamental role in regulating protein stability. The dysregulation ubiquitinating and deubiquitinating enzymes is common feature various cancers, underscoring the imperative to investigate ubiquitin ligases deubiquitinases (DUBs) for insights into oncogenic processes development therapeutic interventions. In this review, we discuss contributions ubiquitin–proteasome system (UPS) all hallmarks cancer progress drug discovery. We delve multiple functions UPS oncology, including its regulation cancer-associated pathways, metabolic reprogramming, engagement with tumor immune responses, function phenotypic plasticity polymorphic microbiomes, other essential cellular functions. Furthermore, provide comprehensive overview novel anticancer strategies that leverage UPS, application proteolysis targeting chimeras (PROTACs) molecular glues.

Язык: Английский

Процитировано

39
Coding, or non-coding, that is the question DOI Creative Commons
Laura Poliseno, Martina Lanza, Pier Paolo Pandolfi

и другие.

Cell Research, Год журнала: 2024, Номер 34(9), С. 609 - 629

Опубликована: Июль 25, 2024

The advent of high-throughput sequencing uncovered that our genome is pervasively transcribed into RNAs are seemingly not translated proteins. It was also found non-coding RNA transcripts outnumber canonical protein-coding genes. This mindboggling discovery prompted a surge in research started unraveling the functional relevance these new genetic units, shaking classic definition "gene". While revolution still taking place, polysome/ribosome profiling and mass spectrometry analyses revealed peptides can be from non-canonical open reading frames. Therefore, it becoming evident coding vs dichotomy way blurrier than anticipated. In this review, we focus on several examples which binary classification genes outdated, since same bifunctional gene expresses both products. We discuss implications intricate usage terms molecular mechanisms expression biological outputs, often concordant, but surprisingly discordant. Finally, methodological caveats associated with study genes, highlight opportunities challenges therapeutic exploitation intricacy towards development anticancer therapies.

Язык: Английский

Процитировано

19
MYC function and regulation in physiological perspective DOI Creative Commons
Rajeev Jha, Fedor Kouzine, David Levens

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Окт. 24, 2023

MYC, a key member of the Myc-proto-oncogene family, is universal transcription amplifier that regulates almost every physiological process in cell including cycle, proliferation, metabolism, differentiation, and apoptosis. MYC interacts with several cofactors, chromatin modifiers, regulators to direct gene expression. levels are tightly regulated, deregulation has been associated numerous diseases cancer. Understanding comprehensive biology under conditions an utmost necessity demark biological functions from its pathological functions. Here we review recent advances mechanisms, functions, regulation MYC. We also emphasize role as global amplifier.

Язык: Английский

Процитировано

29
Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies DOI Creative Commons
Jinze Shen,

Qurui Wang,

Yunan Mao

и другие.

MedComm, Год журнала: 2023, Номер 4(3)

Опубликована: Май 28, 2023

Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, other biological responses. has seven functional domains 12 splice isoforms, different subtypes play roles. The activation inactivation of are finely regulated associated with phosphorylation/acetylation modification ubiquitination modification, respectively. Abnormal is closely related occurrence development cancer. While targeted therapy signaling pathway still its early stages only a few drugs or treatments have entered clinical trials, new ongoing trials expected lead widespread use signaling-targeted cancer treatment future. TRIAP1 novel inhibitor apoptosis. homolog yeast mitochondrial intermembrane protein MDM35, which tumor-promoting role by blocking mitochondria-dependent apoptosis pathway. This work provides systematic overview recent basic research progress proposes that an important therapeutic target signaling.

Язык: Английский

Процитировано

25
Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells DOI Creative Commons
Cristina Trejo‐Solís, Rosa Angélica Castillo‐Rodríguez, Norma Serrano‐García

и другие.

Metabolites, Год журнала: 2024, Номер 14(5), С. 249 - 249

Опубликована: Апрель 25, 2024

The metabolic reprogramming that promotes tumorigenesis in glioblastoma is induced by dynamic alterations the hypoxic tumor microenvironment, as well transcriptional and signaling networks, which result changes global genetic expression. pathways PI3K/AKT/mTOR RAS/RAF/MEK/ERK stimulate cell metabolism, either directly or indirectly, modulating factors p53, HIF1, c-Myc. overexpression of HIF1 c-Myc, master regulators cellular a key contributor to synthesis bioenergetic molecules mediate glioma transformation, proliferation, survival, migration, invasion modifying transcription levels gene groups involved metabolism. Meanwhile, tumor-suppressing protein negatively regulates often lost glioblastoma. Alterations this triad induce shift cells allows them adapt survive such mutations, hypoxia, acidosis, presence reactive oxygen species, nutrient deprivation, activity expression molecules, enzymes, metabolites, transporters, glycolysis glutamine pentose phosphate cycle, tricarboxylic acid oxidative phosphorylation, degradation fatty acids nucleic acids. This review summarizes our current knowledge on role p53 genic regulatory network for metabolism cells, potential therapeutic inhibitors these factors.

Язык: Английский

Процитировано

10
Evolving strategies and application of proteins and peptide therapeutics in cancer treatment DOI Creative Commons
Anirban Goutam Mukherjee, Uddesh Ramesh Wanjari, Abilash Valsala Gopalakrishnan

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 163, С. 114832 - 114832

Опубликована: Май 5, 2023

Several proteins and peptides have therapeutic potential can be used for cancer therapy. By binding to cell surface receptors other indicators uniquely linked with or overexpressed on tumors compared healthy tissue, protein biologics enhance the active targeting of cells, as opposed passive cells by conventional small-molecule chemotherapeutics. This study focuses peptide medications that exist slow stop tumor growth spread cancer, demonstrating in treatment. As an alternative standard chemotherapy, selectively kill while sparing tissue are developing. A mountain clinical evidence supports efficacy peptide-based vaccines. Since a single treatment technique may not sufficient produce favourable results fight against combination therapy is emerging effective option generate synergistic benefits. One example this new area use anticancer nonpeptidic cytotoxic drugs immunotherapy therapies like radiation chemotherapy. review different natural synthetic obtained researched. Discoveries, manufacture, modifications drugs, well their contemporary applications, summarized review. We also discuss benefits difficulties advances peptides.

Язык: Английский

Процитировано

20
Mutant P53 in the formation and progression of the tumor microenvironment: Friend or foe DOI
Elmira Roshani Asl, Davoud Rostamzadeh, Pascal H. G. Duijf

и другие.

Life Sciences, Год журнала: 2023, Номер 315, С. 121361 - 121361

Опубликована: Янв. 4, 2023

Язык: Английский

Процитировано

19
Biological activities of fig latex -loaded cellulose acetate/poly(ethylene oxide) nanofiber for potential therapeutics: Anticancer and antioxidant material DOI
Gomaa El Fawal, Sherien E. Sobhy, E. S. E. Hafez

и другие.

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 270, С. 132176 - 132176

Опубликована: Май 13, 2024

Язык: Английский

Процитировано

6
P53: A key player in diverse cellular processes including nuclear stress and ribosome biogenesis, highlighting potential therapeutic compounds DOI
Gazmend Temaj, Silvia Chichiarelli, Pelin Telkoparan‐Akillilar

и другие.

Biochemical Pharmacology, Год журнала: 2024, Номер 226, С. 116332 - 116332

Опубликована: Июнь 1, 2024

Язык: Английский

Процитировано

5
Expanding Roles of the E2F-RB-p53 Pathway in Tumor Suppression DOI Creative Commons

Yaxuan Zhou,

Rinka Nakajima,

Mashiro Shirasawa

и другие.

Biology, Год журнала: 2023, Номер 12(12), С. 1511 - 1511

Опубликована: Дек. 11, 2023

The transcription factor E2F links the RB pathway to p53 upon loss of function pRB, thereby playing a pivotal role in suppression tumorigenesis. fulfills major cell proliferation by controlling variety growth-associated genes. activity is controlled tumor suppressor which binds and actively suppresses target gene expression, restraining proliferation. Signaling pathways originating from growth stimulative suppressive signals converge on pRB (the pathway) regulate activity. In most cancers, compromised oncogenic mutations, enhanced, facilitating promote Upon such events, activates Arf gene, leading activation protect cells ARF inactivates MDM2, facilitates degradation through proteasome ubiquitination pathway). P53 tumorigenesis inducing cellular senescence or apoptosis. Hence, almost all also disabled. Here we will introduce canonical functions RB-E2F-p53 first then non-classical each component, may be relevant cancer biology.

Язык: Английский

Процитировано

12