The Hallmarks of Glioblastoma: Heterogeneity, Intercellular Crosstalk and Molecular Signature of Invasiveness and Progression

Biomedicines, Journal Year: 2022, Volume and Issue: 10(4), P. 806 - 806

Published: March 30, 2022

In 2021 the World Health Organization published fifth and latest version of Central Nervous System tumors classification, which incorporates summarizes a long list updates from Consortium to Inform Molecular Practical Approaches CNS Tumor Taxonomy work. Among adult-type diffuse gliomas, glioblastoma represents most primary brain in neuro-oncology practice adults. Despite massive efforts field diagnostics ensure proper taxonomy, identification glioblastoma-tumor subtypes is not accompanied by personalized therapies, no improvements terms overall survival have been achieved so far, confirming existence open unresolved issues. The aim this review illustrate elucidate state art regarding foremost biological molecular mechanisms that guide beginning progression cancer, showing salient features tumor hallmarks glioblastoma. Pathophysiology processes are discussed on cellular levels, highlighting critical overlaps involved into creation complex microenvironment. description shows how tumoral can be linked together, finding their involvement within distinct areas engaged for cancer-malignancy establishment maintenance. evidence presented provides promising view interconnected may led better understanding pathophysiology, therefore driving development new therapeutic strategies approaches.

Language: Английский

---

Phosphorylation-Dependent Regulation of WNT/Beta-Catenin Signaling

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: March 14, 2022

WNT/β-catenin signaling is a highly complex pathway that plays diverse roles in various cellular processes. While WNT ligands usually signal through their dedicated Frizzled receptors, the decision to β-catenin-dependent or -independent manner rests upon type of co-receptors used. Canonical β-catenin-dependent, whereas non-canonical β-catenin-independent according classical definition. This still holds true, albeit with some added complexity, as both pathways seem cross-talk intertwined networks involve use different ligands, and co-receptors. β-catenin can be directly phosphorylated by kinases governing its participation either canonical pathways. Moreover, co-activators associate determine output terms induction genes promoting proliferation differentiation. In this review, we provide an overview how protein phosphorylation controls signaling, particularly human cancer.

Language: Английский

---

The strategic roles of four enzymes in the interconnection between metabolism and oncogene activation in non-small cell lung cancer: Therapeutic implications

Drug Resistance Updates, Journal Year: 2022, Volume and Issue: 63, P. 100852 - 100852

Published: July 1, 2022

Language: Английский

---

Hexokinases in cancer and other pathologies

Cell Insight, Journal Year: 2023, Volume and Issue: 2(1), P. 100077 - 100077

Published: Jan. 3, 2023

Glucose metabolism is indispensable for cell growth and survival. Hexokinases play pivotal roles in glucose through canonical functions of hexokinases as well immune response, stemness, autophagy, other cellular activities noncanonical functions. The aberrant regulation contributes to the development progression pathologies, including cancer diseases.

Language: Английский

---

CK2 and the Hallmarks of Cancer

Biomedicines, Journal Year: 2022, Volume and Issue: 10(8), P. 1987 - 1987

Published: Aug. 16, 2022

Cancer is a leading cause of death worldwide. Casein kinase 2 (CK2) commonly dysregulated in cancer, impacting diverse molecular pathways. CK2 highly conserved serine/threonine kinase, constitutively active and ubiquitously expressed eukaryotes. With over 500 known substrates being estimated to be responsible for up 10% the human phosphoproteome, it significant importance. A broad spectrum types cancer cells has been already shown rely on disturbed levels their survival. The hallmarks provide rationale understanding cancer's common traits. They constitute maintenance proliferative signaling, evasion growth suppressors, resisting cell death, enabling replicative immortality, induction angiogenesis, activation invasion metastasis, as well avoidance immune destruction dysregulation cellular energetics. In this work, we have compiled evidence from literature suggesting that modulates all thereby promoting oncogenesis operating driver by creating environment favorable neoplasia.

Language: Английский

---

Butyrate prevents the migration and invasion, and aerobic glycolysis in gastric cancer via inhibiting Wnt/β‐catenin/c‐Myc signaling

Drug Development Research, Journal Year: 2023, Volume and Issue: 84(3), P. 527 - 536

Published: Feb. 13, 2023

Gastric cancer (GC) remains a common cause of death worldwide. Evidence has found that butyrate exhibited antitumor effects on GC cells. However, the mechanism by which regulate cell proliferation, migration, invasion, and aerobic glycolysis largely unknown. The invasion cells were tested EdU staining, transwell assays. Additionally, protein expressions determined western blot assay. Next, glucose uptake, lactate production, cellular ATP levels in detected. Furthermore, tumor-bearing nude mice evaluated. We found, significantly prevented (p < .01). markedly inhibited glycolysis, as shown reduced GLUT1, HK2, LDHA Moreover, notably decreased nuclear β-catenin c-Myc Remarkably, through activating Wnt/β-catenin signaling with LiCl, inhibitory growth diminished suppressed tumor volume weight xenograft vivo Meanwhile, obviously β-catenin, c-Myc, HK2 tissues Collectively, could suppress vitro via downregulating wnt/β-catenin/c-Myc signaling. These findings are likely to prove useful better understanding role GC.

Language: Английский

---

Atherosclerosis, Diabetes Mellitus, and Cancer: Common Epidemiology, Shared Mechanisms, and Future Management

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11786 - 11786

Published: July 22, 2023

The involvement of cardiovascular disease in cancer onset and development represents a contemporary interest basic science. It has been recognized, from the most recent research, that metabolic syndrome-related conditions, ranging atherosclerosis to diabetes, elicit many pathways regulating lipid metabolism signaling are also linked same framework multiple potential mechanisms for inducing cancer. Otherwise, dyslipidemia endothelial cell dysfunction may present common or even interdependent changes, similar oncogenic molecules elevated forms However, whether atherosclerotic provides signals promote pre-clinical proliferation malignant cells is an issue requires further understanding, though more questions presented with every answer. Here, we highlight molecular point causal link between glucose homeostasis knowledge these breakthrough pave way application new therapeutic targets implementing interventions clinical practice.

Language: Английский

---

Shaping immune landscape of colorectal cancer by cholesterol metabolites

EMBO Molecular Medicine, Journal Year: 2024, Volume and Issue: 16(2), P. 334 - 360

Published: Jan. 2, 2024

Abstract Cancer immunotherapies have achieved unprecedented success in clinic, but they remain largely ineffective some major types of cancer, such as colorectal cancer with microsatellite stability (MSS CRC). It is therefore important to study tumor microenvironment resistant cancers for developing new intervention strategies. In this study, we identify a metabolic cue that determines the unique immune landscape MSS CRC. Through secretion distal cholesterol precursors, which directly activate RORγt, CRC cells can polarize T toward Th17 well-characterized pro-tumor functions cancer. Analysis large human cohorts revealed an asynchronous pattern biosynthesis CRC, responsible abnormal accumulation precursors. Inhibiting enzyme Cyp51, by pharmacological or genetic interventions, reduced levels intratumoral precursors and suppressed progression through Th17-modulation mechanism preclinical models. Our reveals novel cancer–immune interaction strategy difficult-to-treat

Language: Английский

---

Long non‐coding RNA NEAT1 promotes aerobic glycolysis and progression of cervical cancer through WNT/β‐catenin/PDK1 axis

Cancer Medicine, Journal Year: 2024, Volume and Issue: 13(9)

Published: May 1, 2024

Abstract Background Cervical cancer is one of the most common gynecological cancers. Accumulated evidence shows that long non‐coding RNAs (lncRNAs) play essential roles in cervical occurrence and progression, but their specific functions mechanisms remain to be further explored. Methods The RT‐qPCR assay was used detect expression NEAT1 tissues cell lines. CCK‐8, colony formation, flow cytometry, western blotting, Transwell assays were evaluate impact on malignant behavior cells. Glucose consumption, lactate production, ATP levels, ROS MMP mRNA expressions glycolysis‐related genes tricarboxylic acid cycle‐related detected analyze effect metabolism reprograming PDK1, β‐catenin downstream molecules WNT/β‐catenin signaling pathway cells by RT‐qPCR, immunofluorescence immunohistochemistry assays. Results This study investigated role possible molecular mechanism lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) cancer. Our results showed highly expressed Downregulation inhibited proliferation, migration, invasion glycolysis cells, while overexpression led opposite effects. Mechanistically, upregulated pyruvate dehydrogenase kinase (PDK1) through pathway, which enhanced then facilitated metastasis. Furthermore, maintained protein stability did not affect its level. We also excluded direct binding via RNA pull‐down assay. suppressive knockdown invasion, migration rescued overexpression. WNT inhibitor iCRT3 attenuated carcinogenic induced Conclusion In summary, these findings indicated may contribute progression activating WNT/β‐catenin/PDK1 axis.

Language: Английский

---

On the Role of Glycolysis in Early Tumorigenesis—Permissive and Executioner Effects

Cells, Journal Year: 2023, Volume and Issue: 12(8), P. 1124 - 1124

Published: April 10, 2023

Reprogramming energy production from mitochondrial respiration to glycolysis is now considered a hallmark of cancer. When tumors grow beyond certain size they give rise changes in their microenvironment (e.g., hypoxia, mechanical stress) that are conducive the upregulation glycolysis. Over years, however, it has become clear can also associate with earliest steps tumorigenesis. Thus, many oncoproteins most commonly involved tumor initiation and progression upregulate Moreover, recent considerable evidence been reported suggesting upregulated itself, through its enzymes and/or metabolites, may play causative role tumorigenesis, either by acting itself as an oncogenic stimulus or facilitating appearance mutations. In fact, several induced have shown be early tumorigenesis: glycolysis-induced chromatin remodeling, inhibition premature senescence induction proliferation, effects on DNA repair, O-linked N-acetylglucosamine modification target proteins, antiapoptotic effects, epithelial–mesenchymal transition autophagy, angiogenesis. this article we summarize and, following, propose mechanistic model aimed at explaining how such role.

Language: Английский

---