CYP19A1 regulates chemoresistance in colorectal cancer through modulation of estrogen biosynthesis and mitochondrial function DOI Creative Commons
Yang Wang, Qiang Ji, N. Cao

и другие.

Cancer & Metabolism, Год журнала: 2024, Номер 12(1)

Опубликована: Окт. 28, 2024

Abstract Chemoresistance remains a major challenge in the effective treatment of colorectal cancer (CRC), contributing to poor patient outcomes. While molecular mechanisms underlying chemoresistance are complex and multifaceted, emerging evidence suggests that altered mitochondrial function hormone signaling play crucial roles. In this study, we investigated role CYP19A1, key enzyme estrogen biosynthesis, regulating CRC. Using combination vitro functional assays, transcriptomic analysis, clinical data mining, demonstrate CYP19A1 expression is significantly upregulated CRC cells patient-derived samples compared normal controls. Mechanistically, found regulates through modulation I activity, which mediated by CYP19A1-dependent biosynthesis. Notably, targeted inhibition using specific inhibitors effectively reversed chemotherapeutic drugs. Moreover, analysis TCGA dataset revealed high correlates with overall survival chemotherapy-treated patients. Taken together, our findings uncover novel for signaling, highlight potential targeting CYP19A1/estrogen/complex axis as therapeutic strategy overcome improve

Язык: Английский

Oxidative Stress and Cancer Therapy: Controlling Cancer Cells Using Reactive Oxygen Species DOI Open Access

Songhyun Ju,

Manish Kumar Singh,

Sunhee Han

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(22), С. 12387 - 12387

Опубликована: Ноя. 18, 2024

Cancer is a multifaceted disease influenced by various mechanisms, including the generation of reactive oxygen species (ROS), which have paradoxical role in both promoting cancer progression and serving as targets for therapeutic interventions. At low concentrations, ROS serve signaling agents that enhance cell proliferation, migration, resistance to drugs. However, at elevated levels, induce oxidative stress, causing damage biomolecules leading death. cells developed mechanisms manage activating pathways such NRF2, NF-κB, PI3K/Akt. This review explores relationship between cancer, focusing on death like apoptosis, ferroptosis, autophagy, highlighting potential strategies exploit target cells.

Язык: Английский

Процитировано

11

CRIP1 inhibits cutaneous melanoma progression through TFAM-mediated mitochondrial biogenesis DOI Creative Commons
Jianqiang Wu, Lixia Chen,

Pengqiang Wen

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 4, 2025

Язык: Английский

Процитировано

1

Deregulation of mitochondrial gene expression in cancer: mechanisms and therapeutic opportunities DOI
Mariah J. Berner, Steven W. Wall, Gloria V. Echeverria

и другие.

British Journal of Cancer, Год журнала: 2024, Номер 131(9), С. 1415 - 1424

Опубликована: Авг. 14, 2024

Язык: Английский

Процитировано

4

Adipose Stem Cells and Their Interplay with Cancer Cells and Mitochondrial Reservoir: A New Promising Target DOI Open Access
Ayesha Rehman,

Martina Marigliano,

Martina Torsiello

и другие.

Cancers, Год журнала: 2024, Номер 16(15), С. 2769 - 2769

Опубликована: Авг. 5, 2024

Adipose-derived stem cells (ASCs) significantly influence tumor progression within the microenvironment (TME). This review examines pro-tumorigenic roles of ASCs, focusing on paracrine signaling, direct cell–cell interactions, and immunomodulation. ASC-mediated mitochondrial transfer through tunneling nanotubes (TNTs) gap junctions (GJs) plays a significant role in enhancing cancer cell survival metabolism. Cancer with dysfunctional mitochondria acquire from ASCs to meet their metabolic needs thrive TME. Targeting transfer, modulating ASC function, influencing pathways are potential therapeutic strategies. However, challenges like TME complexity, specificity, safety concerns, resistance mechanisms must be addressed. Disrupting ASC–cancer cell–mitochondria axis offers promising approach therapy.

Язык: Английский

Процитировано

3

Mitochondrial DNA Alterations in Glioblastoma and Current Therapeutic Targets DOI Creative Commons
Maher Kurdi, Ahmed K. Bamaga, Alaa Alkhotani

и другие.

Frontiers in Bioscience-Landmark, Год журнала: 2024, Номер 29(10)

Опубликована: Окт. 23, 2024

Metabolic reprogramming within tumor cells involves a shift towards either glycolysis or mitochondrial respiration, depending on the stage of progression. Consequently, irreversible dysfunction mitochondria is considered crucial mechanism driving progression mechanism. While numerous mutations in DNA (mtDNA) have been identified across various types, including glioblastoma, many studies limited scope, focusing small segments mtDNA utilizing sequencing methods with restricted sensitivity. As result, several potentially significant may underestimated, along their heteroplasmic states, which play role determining phenotypic impact mutation. Although both somatic and germline observed different research linked to glioblastoma remains scarce. The genome encodes thirteen protein-coding genes that are essential for proper functioning respiratory complex chains. Alterations function manifest at levels, structural functional changes, impacting mitogenic, hemodynamic, bioenergetic, apoptotic signaling pathways. These alterations often signify reduced efficiency oxidative phosphorylation system energy production cells. glioma development grows, emerged as promising targets therapy aimed overcoming chemoresistance eliminating cancer This brief review outlines association between alteration well current advancements therapeutic strategies targeting alterations.

Язык: Английский

Процитировано

3

Identification of TEFM as a potential therapeutic target for LUAD treatment DOI Creative Commons

Wenxuan Hu,

Jian Yang, Kang Hu

и другие.

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 29, 2024

Abstract Background Molecularly targeted therapies have recently become a hotspot in the treatment of LUAD, with ongoing efforts to identify new effective targets due individual variability. Among these potential targets, mitochondrial transcription elongation factor (TEFM) stands out as crucial molecule involved synthetic transcriptional processing. Dysregulation TEFM has been implicated development various diseases; however, its specific role LUAD remains unclear. Methods We conducted comprehensive analysis expression leveraging data from TCGA database. Subsequently, we validated findings using clinical specimens obtained First Affiliated Hospital Soochow University, employing western blotting and qRT-PCR techniques. Further experimental validation was performed through transfection cells overexpression, knockdown, knockout lentiviruses. The effects on were evaluated both vitro vivo range assays, including CCK-8, colony formation, EdU incorporation, Transwell migration, Tunel assay, flow cytometry, JC-1 staining, xenograft tumour models. Results Our investigation uncovered that exhibited elevated levels co-localization mitochondria. Overexpression facilitated malignant processes cells, whereas silencing notably curbed behaviors induced depolarization, along ROS production, culminating apoptosis. Moreover, absence substantially influenced transcripts respiratory chain complexes. nude mouse tumors further inhibiting markedly hindered tumor growth. Conclusion promotes progression EMT pathway determines apoptosis by affecting complexes, providing therapeutic direction for LUAD-targeted therapy. Graphical

Язык: Английский

Процитировано

1

A turn-on mitochondria-targeted iridium (Ⅲ) Complex-Based probe for glutathione detection and photodynamic therapy of cancer cells DOI
Xueting Mao, Fei Xiao, Tongjian Cai

и другие.

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy, Год журнала: 2024, Номер 329, С. 125579 - 125579

Опубликована: Дек. 11, 2024

Язык: Английский

Процитировано

1

Adenine nucleotide translocase 2 silencing promotes metabolic adaptations and anoikis in P19 embryonal carcinoma stem cells DOI Creative Commons

Gabriela L. Oliveira,

Sandra I. Mota, Paulo J. Oliveira

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 9, 2024

Abstract Cancer stem cells (CSCs) are amongst the group of constituting tumors, being characterized by their strong self-renewal and survival properties. cells, CSCs included, thought to rely mostly on glycolysis, even in presence oxygen, which confers them adaptative advantages. Adenine nucleotide translocator 2 (ANT2), responsible for exchange ADP ATP mitochondrial inner membrane, has been correlated with a higher glycolytic metabolism is known be overexpressed cancer cells. Using P19 embryonal carcinoma (P19SCs) as model, we inhibit ANT2 translation using siRNA. protein levels were shown P19SC when compared differentiated counterparts. Furthermore, showed here that OXPHOS machinery membrane potential compromised after depletion, exhibiting metabolic adaptation towards less oxidative phenotype. Interestingly, hexokinase II downregulated, was also accompanied decreased cell growth, ability form spheroids. Our findings underscore key regulator remodeling CSCs, suggesting its therapeutic target controlling CSC-driven tumor progression. Highlights silencing promotes growth arrest CSCs. depletion modulates HKII levels. induce anoikis resistance P19SCs

Язык: Английский

Процитировано

0

Cancerous Conditions Accelerate the Aging of Skeletal Muscle via Mitochondrial DNA Damage DOI Open Access
Yi Luo,

Rina Fujiwara‐Tani,

Isao Kawahara

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 7060 - 7060

Опубликована: Июнь 27, 2024

Skeletal muscle aging and sarcopenia result in similar changes the levels of markers. However, few studies have examined cancer from perspective aging. Therefore, this study investigated explored its causes vitro vivo. In mouse aging, cachexia, cachexia models, skeletal muscles showed markers including oxidative stress, fibrosis, reduced differentiation potential, telomere shortening. Furthermore, examination mitochondrial DNA revealed a 5 kb deletion major arc; truncation complexes I, IV, V electron transport chain; phosphorylation (OXPHOS). The model demonstrated high high-mobility group box-1 (HMGB1) tumor necrosis factor-α (TNFα) ascites. Continuous administration neutralizing antibodies against HMGB1 TNFα stress abrogated deletion. These results suggest that sarcopenia, caused by inflammatory cytokines leads to damage, which turn decreased OXPHOS promotion

Язык: Английский

Процитировано

0

CYP19A1 regulates chemoresistance in colorectal cancer through modulation of estrogen biosynthesis and mitochondrial function DOI Creative Commons
Yang Wang, Qiang Ji, N. Cao

и другие.

Cancer & Metabolism, Год журнала: 2024, Номер 12(1)

Опубликована: Окт. 28, 2024

Abstract Chemoresistance remains a major challenge in the effective treatment of colorectal cancer (CRC), contributing to poor patient outcomes. While molecular mechanisms underlying chemoresistance are complex and multifaceted, emerging evidence suggests that altered mitochondrial function hormone signaling play crucial roles. In this study, we investigated role CYP19A1, key enzyme estrogen biosynthesis, regulating CRC. Using combination vitro functional assays, transcriptomic analysis, clinical data mining, demonstrate CYP19A1 expression is significantly upregulated CRC cells patient-derived samples compared normal controls. Mechanistically, found regulates through modulation I activity, which mediated by CYP19A1-dependent biosynthesis. Notably, targeted inhibition using specific inhibitors effectively reversed chemotherapeutic drugs. Moreover, analysis TCGA dataset revealed high correlates with overall survival chemotherapy-treated patients. Taken together, our findings uncover novel for signaling, highlight potential targeting CYP19A1/estrogen/complex axis as therapeutic strategy overcome improve

Язык: Английский

Процитировано

0