Convergent inducers and effectors of T cell paralysis in the tumour microenvironment

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

Language: Английский

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The epipliancy journey: Tumor initiation at the mercy of identity crisis and epigenetic drift

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: 1880(3), P. 189307 - 189307

Published: April 2, 2025

Cellular pliancy refers to the unique disposition of different stages cellular differentiation transform when exposed specific oncogenic insults. This concept highlights a strong interconnection between identity and tumorigenesis, implies overcoming epigenetic barriers defining states. Emerging evidence suggests that cell-type-specific response intrinsic extrinsic stresses is modulated by accessibility certain areas genome. Understanding interplay mechanisms, differentiation, insults crucial for deciphering complex nature tumorigenesis developing targeted therapies. Hence, relies on dynamic cooperation context through control, including reactivation such as epithelial-to-mesenchymal transition (EMT). Such mechanisms pathways confer plasticity cell allowing it adapt hostile environment in tumor initiation, thus changing its identity. Indeed, growing cancer disease crisis, whereby differentiated cells lose their defined gain progenitor characteristics. The loss fate commitment central feature appears be prerequisite neoplastic transformation. In this context, EMT-inducing transcription factors (EMT-TFs) cooperate with mitogenic oncoproteins foster malignant aberrant activation EMT-TFs plays an active role initiation alleviating key oncosuppressive endowing stem cell-like properties, ability self-renew, course tumorigenesis. highly phenotypic change occurs concomitantly major epigenome reorganization, component regulation. was initially proposed address fundamental question biology: why are some more likely become cancerous events at particular developmental stages? We propose epipliancy, difference configuration leads transformation following insult. Here, we present recent studies furthering our understanding how landscape may impact modulation during early initiation.

Language: Английский

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Epigenomic disorder and partial EMT impair luminal progenitor integrity in Brca1-associated breast tumorigenesis

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: April 28, 2025

In breast cancer related to the BRCA1 mutation, luminal progenitor cells are believed be of origin, yet how these transform into invasive remain poorly understood. Here, we combine single-cell epigenomic and transcriptomic data reconstitute sequences events in that lead tumorigenesis. Upon deletion Trp53 Brca1, find progenitors display an extensive disorder associated with a loss cell identity. These then progress tumor formation through partial epithelial-to-mesenchymal transition, orchestrated by Snail timely activation immunosuppressive FGF signaling their microenvironment. human samples, pre-tumoral changes can detected early stage, basal-like tumors, which rarely recur, as well normal-like mammary glands mutation carriers who have had cancer. Our study fills critical gaps our understanding BRCA1-driven tumorigenesis, opening perspectives for monitoring individuals high risk.

Language: Английский

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Neutrophil Extracellular Traps Promote Pancreatic Cancer Progression via the STING Pathway

Gastroenterology Research and Practice, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Background: Pancreatic cancer is very susceptible to metastasis with a high mortality. Neutrophil extracellular traps (NETs) have been reported be associated poor prognosis in patients suffering from pancreatic cancer. However, the underlying mechanisms by which NETs facilitate progression remain poorly understood. Methods: The expression of was assessed tissues and plasma samples patients. Neutrophils were isolated blood individuals diagnosed evaluate formation. impact on cells investigated, along series experiments aimed at elucidating interaction between neutrophils cells. Results: had higher levels NETs, formation intensified derived significantly promoted both migration invasion capabilities Furthermore, stimulator interferon genes (STING) signaling pathway stimulated produce interleukin-8 (IL-8), subsequently recruited more mediated further NETs. Conclusions: Our data indicate NETs-cancer aggressive crosstalk Specifically, stimulate tumor secrete IL-8, thereby promoting NETosis within microenvironment. Consequently, may key target for treatment.

Language: Английский

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Dynamics of epithelial–mesenchymal plasticity driving cancer drug resistance

Cancer Pathogenesis and Therapy, Journal Year: 2024, Volume and Issue: 3(2), P. 120 - 128

Published: July 6, 2024

Epithelial–mesenchymal transition (EMT) promotes several cancers by increasing tumor cell motility, disrupting epithelial phenotypes, apical–basal polarity, and intracellular connections, enhancing resistance to immunotherapy chemotherapy. Mesenchymal–epithelial (MET), the opposite of EMT, causes metastasis. EMT drives primary cells, whereas MET inhibits them. Importantly, complex network includes cell–cell interactions in microenvironment. Transcription factors, post-translational regulation, cytokine-mediated signaling, micro RNAs control EMT. In this review, we discussed how molecular mechanisms, signaling networks, epithelial/mesenchymal states affect cancer treatment Research on chemotherapy problems associated with suggests that targeting might be a potential strategy.

Language: Английский

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A hybrid epithelial-mesenchymal transition program enables basal epithelial cells to bypass stress-induced stasis and contributes to a metaplastic breast cancer progenitor state

Breast Cancer Research, Journal Year: 2024, Volume and Issue: 26(1)

Published: Dec. 18, 2024

Language: Английский

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