Tuning Push–Pull Electronic Effects of AIEgens to Boost the Theranostic Efficacy for Colon Cancer DOI
Hai‐Tao Feng, Shaomin Zou, Ming Chen

et al.

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(26), P. 11442 - 11450

Published: June 1, 2020

Colon cancer is one of the most common cancers with high mortality in humans. Early diagnosis and treatment colon great significance for therapy. Numerous theranostic agents have been developed to detect kill cells. However, few reports focused on how these control affect gene expression cells vivo. Herein, three pyridinium-functionalized tetraphenylethylene derivatives, namely, TPE-OM, TPE-H, TPE-NO2, electron-donating electron-withdrawing groups were facilely synthesized as cell imaging anticolon Among AIE luminogens (AIEgens), TPE-OM donor acceptor structure showed best efficacy through systematic biological evaluation comparison. Both vitro vivo tumor experiments demonstrated that can be utilized an efficient agent diagnose Flow cytometric analysis revealed cycle process was disturbed by Deep insight into level expressions cell-cycle-promoting genes inhibited upon addition TPE-OM. This study may open a new venue unraveling mechanisms metastasis.

Language: Английский

Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment DOI
Giulia Petroni,

Aitziber Buqué,

Lisa M. Coussens

et al.

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 21(6), P. 440 - 462

Published: March 15, 2022

Language: Английский

Citations

100
SHR and SCR coordinate root patterning and growth early in the cell cycle DOI Creative Commons
Cara M. Winter, Pablo Székely, Vladimir Popov

et al.

Nature, Journal Year: 2024, Volume and Issue: 626(7999), P. 611 - 616

Published: Jan. 31, 2024

Abstract Precise control of cell division is essential for proper patterning and growth during the development multicellular organisms. Coordination formative divisions that generate new tissue patterns with proliferative promote poorly understood. SHORTROOT (SHR) SCARECROW (SCR) are transcription factors required in stem niche Arabidopsis roots 1,2 . Here we show levels SHR SCR early cycle determine orientation plane, resulting either or division. We used 4D quantitative, long-term frequent (every 15 min up to 48 h) light sheet confocal microscopy probe dynamics tandem within single cells living roots. Directly controlling their an induction system enabled us challenge existing bistable model 3 SHR–SCR gene-regulatory network identify key features rescue shr mutants. kinetics do not align expected behaviour a system, only low transient levels, present cycle, divisions. These results reveal uncharacterized mechanism by which developmental regulators directly coordinate growth.

Language: Английский

Citations

22
Decoder-seq enhances mRNA capture efficiency in spatial RNA sequencing DOI
Jiao Cao, Zhong Zheng, Di Sun

et al.

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 16, 2024

Language: Английский

Citations

20
Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy DOI Creative Commons
Matheus Henrique Dias, Anoek Friskes, Siying Wang

et al.

Cancer Discovery, Journal Year: 2024, Volume and Issue: 14(7), P. 1276 - 1301

Published: March 26, 2024

Abstract Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity such aberrant signaling. Although inhibition signaling has been explored extensively, there is increasing evidence overactivation same can also disrupt cancer cause lethality. We show here protein phosphatase 2A (PP2A) hyperactivates multiple engages responses in colon cells. Genetic compound screens identify combined PP2A WEE1 as synergistic models by collapsing DNA replication triggering premature mitosis followed cell death. This combination suppressed growth patient-derived tumors vivo. Remarkably, acquired resistance to this drug ability cells form Our data suggest paradoxical activation result tumor-suppressive resistance. Significance: A therapy consisting deliberate hyperactivation with perturbation from very effective animal cancer. Resistance associated loss reduced capacity, indicative

Language: Английский

Citations

17
LKB1 inactivation promotes epigenetic remodeling-induced lineage plasticity and antiandrogen resistance in prostate cancer DOI Creative Commons
Fei Li,

Pengfei Dai,

Huili Shi

et al.

Cell Research, Journal Year: 2025, Volume and Issue: 35(1), P. 59 - 71

Published: Jan. 2, 2025

Epigenetic regulation profoundly influences the fate of cancer cells and their capacity to switch between lineages by modulating essential gene expression, thereby shaping tumor heterogeneity therapy response. In castration-resistant prostate (CRPC), intricacies behind androgen receptor (AR)-independent lineage plasticity remain unclear, leading a scarcity effective clinical treatments. Utilizing single-cell RNA sequencing on both human mouse samples, combined with whole-genome bisulfite multiple genetically engineered models, we investigated molecular mechanism AR-independent uncovered potential therapeutic strategy. Single-cell transcriptomic profiling cancers, pre- post-androgen deprivation therapy, revealed an association liver kinase B1 (LKB1) pathway inactivation AR independence. LKB1 led global DNA hypomethylation during progression. Importantly, pharmacological inhibition TET enzymes supplementation S-adenosyl methionine were found effectively suppress growth. These insights shed light driving propose strategy targeting in CRPC.

Language: Английский

Citations

2
MUC1-C regulates lineage plasticity driving progression to neuroendocrine prostate cancer DOI Creative Commons
Yota Yasumizu,

Hasan Rajabi,

Caining Jin

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Jan. 17, 2020

Abstract Neuroendocrine prostate cancer (NEPC) is an aggressive malignancy with no effective targeted therapies. The oncogenic MUC1-C protein overexpressed in castration-resistant (CRPC) and NEPC, but its specific role unknown. Here, we demonstrate that upregulation of androgen-dependent PC cells suppresses androgen receptor (AR) axis signaling induces the neural BRN2 transcription factor. activates a MYC→BRN2 pathway association induction MYCN, EZH2 NE differentiation markers (ASCL1, AURKA SYP) linked to NEPC progression. Moreover, p53 pathway, Yamanaka pluripotency factors (OCT4, SOX2, KLF4 MYC) drives stemness. Targeting decreases self-renewal capacity tumorigenicity, suggesting potential therapeutic approach for CRPC NEPC. In tissues, MUC1 expression associates suppression AR increases score. These results highlight as master effector lineage plasticity driving progression

Language: Английский

Citations

125
The oncofetal RNA-binding protein IGF2BP1 is a druggable, post-transcriptional super-enhancer of E2F-driven gene expression in cancer DOI Creative Commons
Simon Müller, Nadine Bley,

Bianca Busch

et al.

Nucleic Acids Research, Journal Year: 2020, Volume and Issue: 48(15), P. 8576 - 8590

Published: Aug. 4, 2020

The IGF2 mRNA-binding protein 1 (IGF2BP1) is a non-catalytic post-transcriptional enhancer of tumor growth upregulated and associated with adverse prognosis in solid cancers. However, conserved effector pathway(s) the feasibility targeting IGF2BP1 cancer remained elusive. We reveal that E2F-driven hallmark promotes G1/S cell cycle transition by stabilizing mRNAs encoding positive regulators this checkpoint like E2F1. This IGF2BP1-driven shortening G1 phase relies on 3'UTR-, miRNA- m6A-dependent regulation suggests enhancement progression m6A-modifications across In addition to E2F transcription factors, also stabilizes transcripts directly indicating 'super'-enhancer role gene expression cancer. small molecule BTYNB disrupts function impairing IGF2BP1-RNA association. Consistently, interferes experimental mouse models.

Language: Английский

Citations

123
Immunomodulation by anticancer cell cycle inhibitors DOI
Giulia Petroni, Silvia C. Formenti, Selina Chen‐Kiang

et al.

Nature reviews. Immunology, Journal Year: 2020, Volume and Issue: 20(11), P. 669 - 679

Published: April 28, 2020

Language: Английский

Citations

120
Transcription Factors in Cancer Development and Therapy DOI Open Access
Kanchan Vishnoi, Navin Viswakarma, Ajay Rana

et al.

Cancers, Journal Year: 2020, Volume and Issue: 12(8), P. 2296 - 2296

Published: Aug. 15, 2020

Cancer is a multi-step process and requires constitutive expression/activation of transcription factors (TFs) for growth survival. Many the TFs reported so far are critical carcinogenesis. These include pro-inflammatory TFs, hypoxia-inducible (HIFs), cell proliferation epithelial-mesenchymal transition (EMT)-controlling pluripotency upregulated in cancer stem-like cells, nuclear receptors (NRs). Some those, including HIFs, Myc, ETS-1, β-catenin, multifunctional may regulate multiple other involved various pro-oncogenic events, proliferation, survival, metabolism, invasion, metastasis. High expression some also correlated with poor prognosis chemoresistance, constituting significant challenge treatment. Considering pivotal role cancer, there an urgent need to develop strategies targeting them. Targeting combination chemotherapeutics, could emerge as better strategy target cancer. So far, NRs have shown promising results improving In this review, we provide comprehensive overview that play central progression, which be potential therapeutic candidates developing specific inhibitors. Here, discuss efforts made those NRs.

Language: Английский

Citations

114
Dying tumor cell-derived exosomal miR-194-5p potentiates survival and repopulation of tumor repopulating cells upon radiotherapy in pancreatic cancer DOI Creative Commons
Mingjie Jiang, Yiyun Chen,

Juanjuan Dai

et al.

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: March 30, 2020

Abstract Background Tumor repopulation is a major cause of radiotherapy failure. Previous investigations highlighted that dying tumor cells played vital roles in through promoting proliferation the residual repopulating (TRCs). However, TRCs also suffer DNA damage after radiotherapy, and might undergo mitotic catastrophe under stimulation proliferative factors released by cells. Hence, we intend to find out how these paradoxical biological processes coordinated potentiate radiotherapy. Methods models vitro vivo were used for evaluating therapy response dissecting underlying mechanisms. RNA-seq was performed signaling changes identify significantly changed miRNAs. qPCR, western blot, IHC, FACS, colony formation assay, etc. carried analyze molecules Results Exosomes derived from induced G1/S arrest promoted survival delivering miR-194-5p, which further modulated E2F3 expression. Moreover, exosomal miR-194-5p alleviated harmful effects oncogenic HMGA2 After latent time, large amount PGE2 boost recovered TRCs, orchestrated cascades. Of note, low-dose aspirin found suppress pancreatic cancer upon radiation via inhibiting secretion exosomes PGE2. Conclusion Exosomal enhanced repopulation. Combined use benefit patients.

Language: Английский

Citations

102