Calpain 2 Isoform‐Specific Cleavage of Filamin A Enhances HIF1α Nuclear Translocation, Promoting Metastasis in Triple‐Negative Breast Cancer DOI Creative Commons
Kyung‐Hwa Jeon, Seojeong Park,

Eun Seon Pak

и другие.

MedComm, Год журнала: 2025, Номер 6(4)

Опубликована: Март 27, 2025

Triple-negative breast cancer (TNBC) remains a challenge due to its aggressive nature and limited therapeutic options. Calpain 2, member of the calcium-dependent cysteine protease family, is particularly associated with poor prognosis in TNBC. This study explores isoform-specific role calpain 2 TNBC, examining correlation mechanistic impact on metastasis. Bioinformatic analyses, including Kaplan-Meier survival plots, univariate Cox proportional analysis, gene set enrichment analysis (GSEA), assessed CAPN2 expression association mesenchymal genes Results cell-based experiments knockdown or overexpression indicate that elevated correlates clinical outcomes enhanced metastatic potential inhibited epithelial-mesenchymal transition (EMT), reducing cell proliferation, migration, invasion. downregulation reversed EMT by cleavage filamin A, HIF1α nuclear localization TWIST1 transcription. CNa 29, 2-specific inhibitor, reduced decreased A cleavage, downregulated expression, significantly retarded metastasis,. In conclusion, plays critical TNBC progression modulating TWIST1, promote Isoform-selective inhibition 29 presents promising strategy for managing

Язык: Английский

Invasion and metastasis in cancer: molecular insights and therapeutic targets DOI Creative Commons

Yongxing Li,

Fengshuo Liu,

Qingjin Cai

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 20, 2025

The progression of malignant tumors leads to the development secondary in various organs, including bones, brain, liver, and lungs. This metastatic process severely impacts prognosis patients, significantly affecting their quality life survival rates. Research efforts have consistently focused on intricate mechanisms underlying this corresponding clinical management strategies. Consequently, a comprehensive understanding biological foundations tumor metastasis, identification pivotal signaling pathways, systematic evaluation existing emerging therapeutic strategies are paramount enhancing overall diagnostic treatment capabilities for tumors. However, current research is primarily metastasis within specific cancer types, leaving significant gaps our complex cascade, organ-specific tropism mechanisms, targeted treatments. In study, we examine sequential processes elucidate driving organ-tropic systematically analyze tumors, those tailored organ involvement. Subsequently, synthesize most recent advances technologies challenges opportunities encountered pertaining bone metastasis. Our objective offer insights that can inform future practice crucial field.

Язык: Английский

Процитировано

7
A new peptide inhibitor of C1QBP exhibits potent anti‐tumour activity against triple negative breast cancer by impairing mitochondrial function and suppressing homologous recombination repair DOI Creative Commons
Xingxing Li, Yue Wu, Min Zhang

и другие.

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 1, 2025

Abstract C1QBP exhibits heightened expression across a spectrum of tumours, thereby fostering their proliferation and metastasis, rendering it pivotal therapeutic target. Nevertheless, to date, no pharmacological agents capable directly targeting inducing the degradation have been identified. In this study, we unveiled new peptide, PDBAG1, derived from precursor protein GPD1, employing peptidomics‐based drug screening strategy. PDBAG1 has demonstrated substantial efficacy in suppressing triple‐negative breast cancer (TNBC) both vitro vivo. Its mechanism action involves mitochondrial impairment inhibition oxidative phosphorylation (OXPHOS), achieved through direct binding C1QBP, promoting its ubiquitin‐dependent degradation. Concomitantly, due metabolic adaptability, observed an up‐regulation glycolysis compensate for OXPHOS inhibition. We aberrant phenomenon wherein hypoxia signalling pathway tumour cells exhibited significant activation under normoxic conditions following treatment. Through size‐exclusion chromatography (SEC) isothermal titration calorimetry (ITC) assays, validated that is with K d value 334 nM. Furthermore, inhibits homologous recombination repair proteins facilitates synergism poly‐ADP‐ribose polymerase inhibitors therapy. This underscores ultimately induces insurmountable survival stress multiple mechanisms while concurrently engendering vulnerabilities specific TNBC. Key points The newly discovered peptide first small molecule substance found target degrade demonstrating inhibitory effects potential.

Язык: Английский

Процитировано

2
Pseudostellaria heterophylla (Miq.) Pax, a Traditional Folk Medicine, Ameliorates Colorectal Cancer by Remodeling the Tumor Immune Microenvironment DOI
Gui Yang, Hui Wu, Heng Fan

и другие.

Journal of Ethnopharmacology, Год журнала: 2025, Номер 342, С. 119362 - 119362

Опубликована: Янв. 17, 2025

Язык: Английский

Процитировано

1
An update on promising and emerging protein kinase B/AKT inhibitors for breast cancer DOI Creative Commons

Riccardo Asnaghi,

Gabriele Antonarelli,

Elena Battaiotto

и другие.

Expert Opinion on Pharmacotherapy, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Introduction . The PI3K pathway is crucial in breast cancer (BC), influencing cell survival, growth, and metabolism, with AKT playing a central role treatment resistance. This pathway's involvement carcinogenesis its link to resistance underscores the significance of targeting it BC therapy. PI3K-pathway inhibitors offer new therapeutic avenues but bring challenges, especially due toxicity issues that hinder their development.

Язык: Английский

Процитировано

1
Increasing RB1 Expression by Targeting EZH2 in Triple‐Negative Breast Cancer DOI Creative Commons

Rui Yang,

Liyan Fei, Yingfei Xue

и другие.

Journal of Cellular and Molecular Medicine, Год журнала: 2025, Номер 29(5)

Опубликована: Март 1, 2025

ABSTRACT Loss of RB1 function represents a defining characteristic triple‐negative breast cancer (TNBC) and is intricately associated with resistance to therapeutic interventions. In this study, we investigate the epigenetic mechanisms governing expression in TNBC. Employing combination bioinformatics analyses experimental validations, identified lysine histone methyltransferase EZH2 as key upstream regulator expression. primarily mediates trimethylation 27 on H3 catalytic subunit Polycomb repressive complex 2 (PRC2) complex. Furthermore, our findings demonstrate that pharmacological inhibition leads significant upregulation levels, mediated by enhanced enrichment activating marker H3K27ac at enhancer region, evidenced ATAC‐sequencing ChIP‐qPCR assays. These insights unveil promising clinical avenue for combating RB1‐mediated drug TNBC through strategic integration epigenetic‐targeting agents.

Язык: Английский

Процитировано

1
Nanoconjugate Carrying pH-Responsive Transferrin Receptor-Targeted Hesperetin Triggers Triple-Negative Breast Cancer Cell Death through Oxidative Attack and Assemblage of Pro-Apoptotic Proteins DOI

Dibyendu Giri,

Surya Kanta Dey,

Sounik Manna

и другие.

ACS Applied Bio Materials, Год журнала: 2024, Номер 7(11), С. 7556 - 7573

Опубликована: Ноя. 6, 2024

Triple-negative breast cancer (TNBC) is recognized as a major aggressive subtype of due to its expeditious worsening growth, extensive metastatic capability, and recalcitrance standard current treatments. Hesperetin (HSP), natural bioflavonoid from citrus fruits, demonstrates pronounced anticancer efficacy, but hydrophobicity limits clinical development. The present study reports the fabrication biocompatible pH-responsive transferrin (TF) receptor-targeted HSP-loaded poly(lactic-co-glycolic acid) (PLGA) nanobioconjugate (PLGA-HSP-TF NPs) exploration in vitro vivo antineoplastic potential. PLGA nanoparticles (NPs), PLGA-HSP NPs, PLGA-HSP-TF NPs were synthesized characterized by DLS, FTIR, FE-SEM, 1H NMR spectroscopy. stability release profile inspected, efficacy was scrutinized terms cytotoxicity, oxidative stress apoptosis biomarkers, cell cycle arrest. In tumor regression host survival studies executed Ehrlich ascites carcinoma (EAC) cell-bearing Swiss albino mice. drug uptake highly stable accomplished effectively MDA-MB-231 cells showed pH-dependent intracellular HSP, which generated excessive reactive oxygen species (ROS) that led assault TNBC cells. This elevated ROS dropped mitochondrial membrane potential triggered apoptosis-mediated death arresting at G0/G1 phase. Furthermore, unveiled significant compared free HSP with minimum toxicity dose 20 mg/kg body weight. divulges may be an astounding nanocandidate for triple-negative therapy.

Язык: Английский

Процитировано

4
Fibroblast Growth Factor Receptor 4 Promotes Triple‐Negative Breast Cancer Progression via Regulating Fatty Acid Metabolism Through the AKT/RYR2 Signaling DOI Creative Commons

Jinhui Ye,

Song Wu,

Qiang Quan

и другие.

Cancer Medicine, Год журнала: 2024, Номер 13(23)

Опубликована: Дек. 1, 2024

Triple-negative breast cancer (TNBC) is the most aggressive subtype of cancer. Previous studies have found that fibroblast growth factor receptor 4 (FGFR4) plays a crucial role in tumor development and metastasis. However, potential underlying mechanisms FGFR4 progression TNBC remain unclear.

Язык: Английский

Процитировано

4
Studying the effects of Saposhnikoviae Radix on the pharmacokinetic profiles of 10 bioactive compounds originating from Astragali Radix in rat plasma by UHPLC-QTRAP-MS/MS DOI

Lin-Han Xiang,

Meng-Ge Feng,

Xu-Yan Guo

и другие.

Journal of Ethnopharmacology, Год журнала: 2024, Номер unknown, С. 118813 - 118813

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

3
YTHDF2 promotes anaplastic thyroid cancer progression by activating the DDIT4/AKT/mTOR signaling pathway DOI Creative Commons

Bao Dai,

Lei Xu, Shikuo Rong

и другие.

Biology Direct, Год журнала: 2024, Номер 19(1)

Опубликована: Ноя. 26, 2024

Abstract Background RNA methylation, an important reversible post-transcriptional modification in eukaryotes, has emerged as a prevalent epigenetic alteration. However, the role of m6A reader YTH domain family 2 (YTHDF2) not been reported anaplastic thyroid cancer (ATC) and its biological mechanism is unclear. Methods The relationship between YTHDF2 expression ATC was determined using data sets tissue samples. A range analytical techniques were employed to investigate regulatory ATC, including bioinformatics analysis, dot-blot methylated immunoprecipitation sequencing (MeRIP-seq), (RIP) assays, sequencing, stability assays dual luciferase reporter gene assays. In vitro vivo also conducted determine contribution development. Results significantly increased ATC. comprehensive experiments demonstrated that knockdown attenuated proliferation, invasion, migration, apoptosis promotion, whereas overexpression yielded opposite trend. Mechanistically, RNA-seq, MeRIP-seq RIP-seq molecular biology accelerated degradation DNA damage-inducible transcript 4 or regulated damage development 1 (DDIT4, REDD1) mRNA m6A-dependent manner, which turn activated AKT/mTOR signaling pathway induced activation epithelial-mesenchymal transition (EMT), thereby promoting tumor progression. Conclusions This study first demonstrate elevated levels suppress DDIT4 manner activate pathway, plays pivotal progression, it may serve promising therapeutic target future.

Язык: Английский

Процитировано

3
Ononin Inhibits Tumor Bone Metastasis and Osteoclastogenesis Via Targeting MAPK Pathway in Breast Cancer DOI Creative Commons
Kumar Ganesan, Cong Xu, Song Wu

и другие.

Research, Год журнала: 2024, Номер 7

Опубликована: Янв. 1, 2024

Breast cancer (BC) often spreads to bones, leading bone metastasis (BM). Current targeted therapies have limited effectiveness in the treatment of this condition. Osteoclasts, which contribute destruction, are crucial supporting tumor cell growth bones. (BCBM) treatments efficacy and can cause adverse effects. Ononin exhibits anticancer properties against various cancers. The study examined impact ononin on BCBM signaling pathways involved. Our utilized a variety experimental techniques, including viability assays, colony formation wound-healing Transwell migration Western blot analysis, tartrate-resistant acid phosphatase (TRAP) staining. We effects osteoclastogenesis induced MDA-MB-231 conditioned medium- RANKL-treated RAW 264.7 cells. In mouse model BCBM, reduced tumor-induced destruction. effectively inhibited proliferation metastatic capabilities cells by suppressing adhesion, invasiveness, motility reversing epithelial–mesenchymal transition (EMT) markers. markedly suppressed osteoclast osteolysis-associated factors cells, as well blocked activation mitogen-activated protein kinase (MAPK) pathway down-regulated phosphorylation MAPK pathways, confirmed using agonists or inhibitors. had no organ function. findings suggest that has therapeutic potential targeting pathway.

Язык: Английский

Процитировано

3