Mitophagy: insights into its signaling molecules, biological functions, and therapeutic potential in breast cancer DOI Creative Commons
Cong Chen,

Aizhai Xiang,

Xia Lin

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Oct. 29, 2024

Abstract Mitophagy, a form of selective autophagy that removes damaged or dysfunctional mitochondria, plays crucial role in maintaining mitochondrial and cellular homeostasis. Recent findings suggest defective mitophagy is closely associated with various diseases, including breast cancer. Moreover, better understanding the multifaceted roles cancer progression for treatment this disease. Here, we will summarize molecular mechanisms process. In addition, highlight expression patterns mitophagy-related signaling molecules potential implications development cancer, aiming to provide therapeutic strategies treatment.

Language: Английский

Role of mitochondrial alterations in human cancer progression and cancer immunity DOI Creative Commons
Sheng‐Fan Wang, Ling‐Ming Tseng, Hsin‐Chen Lee

et al.

Journal of Biomedical Science, Journal Year: 2023, Volume and Issue: 30(1)

Published: July 31, 2023

Abstract Dysregulating cellular metabolism is one of the emerging cancer hallmarks. Mitochondria are essential organelles responsible for numerous physiologic processes, such as energy production, metabolism, apoptosis, and calcium redox homeostasis. Although “Warburg effect,” in which cells prefer aerobic glycolysis even under normal oxygen circumstances, was proposed a century ago, how mitochondrial dysfunction contributes to progression still unclear. This review discusses recent progress alterations DNA (mtDNA) dynamics malignant progression. Moreover, we integrate possible regulatory mechanism dysfunction–mediated retrograde signaling pathways, including mitochondrion-derived molecules (reactive species, calcium, oncometabolites, mtDNA) stress response pathways (mitochondrial unfolded protein integrated response) provide therapeutic targets. Furthermore, discuss findings on role mitochondria immune function reveal impact tumor microenvironment remodeling immunity. Targeting might improve immunotherapy. These suggest that targeting malignancy modulating immunity be promising treatment strategies patients precise personalized medicine against cancer.

Language: Английский

Citations

62
NADPH Oxidases: From Molecular Mechanisms to Current Inhibitors DOI Creative Commons
Alessandra Cipriano, Monica Viviano, Alessandra Feoli

et al.

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(17), P. 11632 - 11655

Published: Aug. 31, 2023

NADPH oxidases (NOXs) form a family of electron-transporting membrane enzymes whose main function is reactive oxygen species (ROS) generation. Strong evidence suggests that ROS produced by NOX are major contributors to oxidative damage under pathologic conditions. Therefore, blocking the undesirable actions these therapeutic strategy for treating various pathological disorders, such as cardiovascular diseases, inflammation, and cancer. To date, identification selective inhibitors quite challenging, precluding pharmacologic demonstration targets in vivo. The aim this Perspective furnish an updated outlook about small-molecule described over last two decades. Structures, activities, vitro/in vivo specificity discussed, well biological assays used.

Language: Английский

Citations

58
Examining the function of macrophage oxidative stress response and immune system in glioblastoma multiforme through analysis of single-cell transcriptomics DOI Creative Commons
Xing Jin,

Huabao Cai,

Zhiheng Lin

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 11, 2024

Background Glioblastoma (GBM), a prevalent malignant neoplasm within the neuro-oncological domain, has been subject of considerable scrutiny. Macrophages, serving as principal immunological constituents, profoundly infiltrate microenvironment GBM. However, investigations elucidating intricate mechanisms governing macrophage involvement in GBM at single-cell level remain notably limited. Methods We conducted comprehensive investigation employing analysis, aiming to redefine cellular landscape both core and peripheral regions tumors. Our analytical focus extended profound study macrophages, their roles context oxidative stress, intercellular information exchange, trajectories concerning its assorted subpopulations. pursued identification prognostic genes intricately associated with macrophages. Utilizing experimental research investigate relevance MANBA Results have illuminated central role macrophages interplay among various subpopulations microenvironment. Notably, we observed pronounced intensity stress responses when compared counterparts other Moreover, orchestrated communication networks, facilitated by SPP1-CD44 axis, internally neighboring These findings collectively suggest potential for polarization from an M1 M2 phenotype, contributing immune suppression tumor Furthermore, our exploration unearthed closely most TCF12. Remarkably, appears participate modulation neuroimmune functionality exerting inhibitory effects on M1-polarized thereby fostering progression. To bolster these assertions, validations unequivocally affirmed promotional impact GBM, elucidated through capacity curb cell proliferation, invasiveness, metastatic potential. Conclusion revelations represent pivotal step towards unraveling interactions between diverse milieu. they lay foundation development innovative model, epicenter, underscore novel immunotherapeutic targets ongoing pursuit enhanced treatment modalities this formidable malignancy.

Language: Английский

Citations

45
Deciphering the molecular landscape: integrating single-cell transcriptomics to unravel myofibroblast dynamics and therapeutic targets in clear cell renal cell carcinomas DOI Creative Commons
Wenqian Zhou, Zhiheng Lin, Tan Wang

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 18, 2024

Background Clear cell renal carcinomas (ccRCCs) epitomize the most formidable clinical subtype among neoplasms. While impact of tumor-associated fibroblasts on ccRCC progression is duly acknowledged, a paucity literature exists elucidating intricate mechanisms and signaling pathways operative at individual cellular level. Methods Employing single-cell transcriptomic analysis, we meticulously curated UMAP profiles spanning substantial populations, delving into composition intrinsic these cohorts. Additionally, Myofibroblasts were fastidiously categorized discrete subpopulations, with thorough elucidation temporal trajectory relationships between subpopulations. We further probed interaction connecting pivotal subpopulations tumors. Our endeavor also encompassed identification prognostic genes associated through Bulk RNA-seq, subsequently validated empirical experimentation. Results A notable escalation in nFeature nCount EPCs within ccRCCs was observed, notably enriched oxidation-related pathways. This phenomenon postulated to be closely heightened metabolic activities EPCs. The subpopulation, denoted as C3 HMGA1+ Myofibroblasts, emerges subset, displaying low differentiation positioning itself terminal point trajectory. Intriguingly, cells exhibit high degree tumor MPZ pathway network, suggesting that may facilitate via this pathway. Prognostic identified, which TUBB3 implicated potential resistance recurrence. Finally, experimental validation revealed knockout key gene pathway, MPZL1, can inhibit activity, proliferation, invasion, migration capabilities. Conclusion investigation delves propose targeting MPZL1 oxidative phosphorylation could serve targets for treating recurrence ccRCC. discovery paves way new directions treatment prognosis diagnosis future.

Language: Английский

Citations

28
Tumor-microenvironment-activatable organic phototheranostic agents for cancer therapy DOI

Shuang Zeng,

Zhihan Guo,

Yifu Hao

et al.

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 509, P. 215786 - 215786

Published: March 20, 2024

Language: Английский

Citations

26
Mitochondrial dysfunction route as a possible biomarker and therapy target for human cancer DOI Creative Commons
Rawan Al‐Faze, Hoda A. Ahmed, Mohamed A. El‐Atawy

et al.

Biomedical Journal, Journal Year: 2024, Volume and Issue: unknown, P. 100714 - 100714

Published: March 1, 2024

Mitochondria are vital organelles found within living cells and have signalling, biosynthetic, bioenergetic functions. play a crucial role in metabolic reprogramming, which is characteristic of cancer allows them to assure steady supply proteins, nucleotides, lipids enable rapid proliferation development. Their dysregulated activities been associated with the growth metastasis different kinds human cancer, particularly ovarian carcinoma. In this review, we briefly demonstrated modified mitochondrial function including mutations mtDNA, reactive oxygen species production, dynamics, apoptosis cells, autophagy, calcium excess maintain genesis, progression, metastasis. Furthermore, dysfunction pathway for some genomic, proteomic, metabolomics modifications has studied. Additionally, linked targeted therapies biomarkers through various alteration processes underlying dysfunction, notably targeting species, metabolites, rewind pathways, chemo-resistant carcinoma cells.

Language: Английский

Citations

19
ROS: A “booster” for chronic inflammation and tumor metastasis DOI

Anqi Chen,

Haifeng Huang,

S. S. Fang

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(6), P. 189175 - 189175

Published: Aug. 31, 2024

Language: Английский

Citations

19
Polyproline‐Polyornithine Diblock Copolymers with Inherent Mitochondria Tropism DOI Creative Commons
Camilla Pegoraro, Ekaterina Karpova, Yusuf Qutbuddin

et al.

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Mitochondria play critical roles in regulating cell fate, with dysfunction correlating the development of multiple diseases, emphasizing need for engineered nanomedicines that cross biological barriers. Said often target fluctuating mitochondrial properties and/or present inefficient/insufficient cytosolic delivery (resulting poor overall activity), while many require complex synthetic procedures involving targeting residues (hindering clinical translation). The synthesis/characterization polypeptide‐based penetrating diblock copolymers poly‐L‐ornithine (PLO) and polyproline (PLP) (PLO n ‐PLP m , n:m ratio 1:3) are described as mitochondria‐targeting nanocarriers. Synthesis involves a simple two‐step methodology based on N‐carboxyanhydride ring‐opening polymerization, scale‐up optimization using “design experiments” approach. molecular mechanisms behind targetability therapeutic activity investigated through physical/biological processes themselves or moieties poly‐L‐glutamic (PGA)‐based conjugate. Diblock prompt rapid entry via energy‐independent recognize mitochondria mitochondria‐specific phospholipid cardiolipin (CL). Stimuli‐driven conditions polarization dynamics, which decrease efficacy depending disease type/stage, do not compromise copolymer uptake/targetability. exhibit inherent concentration‐dependent anti‐tumorigenic at level. conjugate possesses improved safety, significant penetration, accumulation recognition. These findings may support efficient safe mitochondrial‐targeting nanomedicines.

Language: Английский

Citations

3
Exploring Strategies to Prevent and Treat Ovarian Cancer in Terms of Oxidative Stress and Antioxidants DOI Creative Commons

Yanru Long,

Houhui Shi,

Jiatian Ye

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 114 - 114

Published: Jan. 20, 2025

Oxidative stress is a state of imbalance between the production reactive oxygen species (ROS) and nitrogen (RNS) antioxidant defence system in body. may be associated with variety diseases, such as ovarian cancer, diabetes mellitus, neurodegeneration. The generation oxidative one common refractory malignancies among gynaecological tumours, several factors. On hand, increased metabolism cancer cells can lead to ROS, on other impaired not able effectively scavenge excessive ROS. In addition, chemotherapy radiotherapy elevate cells. cause damage, promote development even result drug resistance. Therefore, studying important for prevention treatment cancer. Antioxidants, markers stress, might serve strategies preventing treating this review, we will discuss complex relationship well role therapeutic potential antioxidants thus guiding future research clinical interventions.

Language: Английский

Citations

2
Molecular mechanisms of ROS-modulated cancer chemoresistance and therapeutic strategies DOI Open Access
Xiaoting Zhou,

Biao An,

Yi Lin

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 165, P. 115036 - 115036

Published: June 23, 2023

Drug resistance is the main obstacle to achieving a cure in many cancer patients. Reactive oxygen species (ROS) are master regulators of development that act through complex mechanisms. Remarkably, ROS levels and antioxidant content typically higher drug-resistant cells than non-resistant normal cells, have been shown play central role modulating drug resistance. Therefore, determining underlying functions modulation will contribute develop therapies sensitize resistant by leveraging modulation. In this review, we summarize notable literature on sources regulation production highlight roles chemoresistance, encompassing transcription factor-mediated maintenance stem their impact tumor microenvironment. We also discuss potential ROS-targeted overcoming therapeutic

Language: Английский

Citations

39