Cancer cell plasticity defines response to immunotherapy in cutaneous squamous cell carcinoma DOI Creative Commons
Laura Lorenzo-Sanz, Marta Lopez-Cerda, Victoria da Silva-Diz

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 24, 2024

Abstract Immune checkpoint blockade (ICB) approaches have changed the therapeutic landscape for many tumor types. However, half of cutaneous squamous cell carcinoma (cSCC) patients remain unresponsive or develop resistance. Here, we show that, during cSCC progression in male mice, cancer cells acquire epithelial/mesenchymal plasticity and change their immune (IC) ligand profile according to features, dictating IC pathways involved evasion. Epithelial cells, through PD-1/PD-L1 pathway, mesenchymal CTLA-4/CD80 TIGIT/CD155 pathways, differentially block antitumor responses determine response ICB therapies. Accordingly, anti-PD-L1/TIGIT combination is most effective strategy blocking growth cSCCs that contain both epithelial cells. The expression E-cadherin/Vimentin/CD80/CD155 proteins cSCC, HNSCC melanoma patient samples predicts anti-PD-1/PD-L1 therapy. Collectively, our findings indicate selection therapies should take into account features

Language: Английский

Fibroblasts in cancer: Unity in heterogeneity DOI Creative Commons
Yash Chhabra, Ashani T. Weeraratna

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1580 - 1609

Published: April 1, 2023

Language: Английский

Citations

197
Gallbladder cancer DOI
Juan Carlos Roa, Patricia García, Vinay K. Kapoor

et al.

Nature Reviews Disease Primers, Journal Year: 2022, Volume and Issue: 8(1)

Published: Oct. 27, 2022

Language: Английский

Citations

193
Heterogeneity and plasticity of epithelial–mesenchymal transition (EMT) in cancer metastasis: Focusing on partial EMT and regulatory mechanisms DOI Creative Commons

Dandan Li,

Lingyun Xia,

Pan Huang

et al.

Cell Proliferation, Journal Year: 2023, Volume and Issue: 56(6)

Published: Feb. 19, 2023

Epithelial-mesenchymal transition (EMT) or mesenchymal-epithelial (MET) plays critical roles in cancer metastasis. Recent studies, especially those based on single-cell sequencing, have revealed that EMT is not a binary process, but heterogeneous and dynamic disposition with intermediary partial states. Multiple double-negative feedback loops involved by EMT-related transcription factors (EMT-TFs) been identified. These between drivers MET finely regulate the state of cell. In this review, general characteristics, biomarkers molecular mechanisms different states were summarized. We additionally discussed direct indirect tumour More importantly, article provides evidence heterogeneity closely related to poor prognosis gastric cancer. Notably, seesaw model was proposed explain how cells themselves remain specific states, including epithelial state, hybrid/intermediate mesenchymal state. Additionally, also review current status, limitations future perspectives signalling clinical applications.

Language: Английский

Citations

78
Epithelial–Mesenchymal Plasticity in Tumor Immune Evasion DOI Open Access
Riley Mullins, Ananya Pal, Thomas F. Barrett

et al.

Cancer Research, Journal Year: 2022, Volume and Issue: 82(13), P. 2329 - 2343

Published: April 1, 2022

Epithelial-mesenchymal transition (EMT) is a fundamental process that occurs during embryogenesis and tissue repair. However, EMT can be hijacked by malignant cells, where it may promote immune evasion metastasis. Classically considered dichotomous transition, in cancer has recently been plastic whereby cells display interconvert among hybrid epithelial/mesenchymal (E/M) states. plasticity (EMP) associated E/M states are divergent from classical EMT, with unique immunomodulatory effects. Here, we review recent insights into the EMP-immune cross-talk, highlighting possible mechanisms of conferred roles EMP.

Language: Английский

Citations

40
Clinical impact of epithelial–mesenchymal transition for cancer therapy DOI Creative Commons
Nobendu Mukerjee, Sagnik Nag, Bikramjit Bhattacharya

et al.

Clinical and Translational Discovery, Journal Year: 2024, Volume and Issue: 4(1)

Published: Jan. 28, 2024

Abstract The epithelial–mesenchymal transition (EMT) represents a pivotal frontier in oncology, playing central role the metastatic cascade of cancer—a leading global health challenge. This comprehensive review delves into complexities EMT, process where cancer cells gain exceptional mobility, facilitating their invasion distant organs and establishment secondary malignancies. We thoroughly examine myriad factors influencing encompassing transcription factors, signalling pathways, metabolic alterations, microRNAs, long non‐coding RNAs, epigenetic changes, exosomal interactions intricate dynamics tumour microenvironment. Particularly, emphasises advanced stages crucial for development highly aggressive phenotypes. During this phase, penetrate vascular barrier exploit bloodstream to propagate life‐threatening metastases through mesenchymal–epithelial transition. also explore EMT's significant fostering dormancy, senescence, emergence stem formidable challenge therapeutic resistance. Our transcends mere inventory EMT‐inducing elements; it critically assesses current state EMT‐focused clinical trials, revealing both hurdles breakthroughs. Highlighting potential EMT research, we project its transformative impact on future therapy. exploration is aimed at paving way towards an era effectively managing relentless disease, positioning forefront innovative research strategies.

Language: Английский

Citations

11
Intratumour oxidative hotspots provide a niche for cancer cell dissemination DOI
Yoshifumi Ueda, Shigeki Kiyonaka, Laura M. Selfors

et al.

Nature Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Language: Английский

Citations

1
The Inflammatory Profile of the Tumor Microenvironment, Orchestrated by Cyclooxygenase-2, Promotes Epithelial-Mesenchymal Transition DOI Creative Commons
Fernán Gómez‐Valenzuela, Enrico Escobar, Ricardo Pérez‐Tomás

et al.

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: June 10, 2021

The tumor microenvironment (TME) corresponds to a complex and dynamic interconnection between the extracellular matrix malignant cells their surrounding stroma composed of immune mesenchymal cells. TME has constant cellular communication through cytokines that sustain an inflammatory profile, which favors progression, angiogenesis, cell invasion, metastasis. Although epithelial-mesenchymal transition (EMT) represents relevant metastasis-initiating event promotes invasive phenotype in epithelial cells, its relationship with profile is poorly understood. Previous evidence strongly suggests cyclooxygenase-2 (COX-2) overexpression, pro-inflammatory enzyme related chronic unresolved inflammation, associated common EMT-signaling pathways. This review article summarizes how COX-2 within context TME, orchestrates EMT process initial metastatic-related events.

Language: Английский

Citations

50
Research progress on the anti-tumor effect of Naringin DOI Creative Commons

Jing He,

Huiping Zhang

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 17, 2023

Naringin is a kind of natural dihydro flavone, which mainly exists in citrus fruits the Rutaceae family, as well traditional Chinese medicines such trifoliate orange, fingered citron, exocarpium citri grandis, and rhizoma dynamite. Modern pharmacological studies have shown that has excellent anti-tumor activity. Through reviewing relevant literature at home abroad recent years, we summarized mechanism to play an anti-cancer role blocking tumor cell cycle, inhibiting proliferation, inducing apoptosis, invasion metastasis, autophagy, reversing drug resistance enhancing chemotherapeutic sensitivity, anti-inflammatory prevent canceration, alleviate Adverse reaction chemotherapy, activate strengthen immunity, It provides theoretical basis reference for further exploring anticancer potential its development utilization.

Language: Английский

Citations

19
VC-resist glioblastoma cell state: vessel co-option as a key driver of chemoradiation resistance DOI Creative Commons

Cathy Pichol-Thievend,

Océane Anezo,

Aafrin M. Pettiwala

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 29, 2024

Abstract Glioblastoma (GBM) is a highly lethal type of cancer. GBM recurrence following chemoradiation typically attributed to the regrowth invasive and resistant cells. Therefore, there pressing need gain deeper understanding mechanisms underlying resistance its ability infiltrate. Using combination transcriptomic, proteomic, phosphoproteomic analyses, longitudinal imaging, organotypic cultures, functional assays, animal studies, clinical data we demonstrate that brain vasculature induce cell transition state named VC-Resist (vessel co-opting state). This midway along transcriptomic axis between proneural mesenchymal cells closer AC/MES1-like state. are vessel co-opting, allowing significant infiltration into surrounding tissue homing perivascular niche, which in turn induces even more transition. The molecular characteristics this FGFR1-YAP1-dependent state, including DNA damage, enrichment G2M phase, induction senescence/stemness pathways, contribute enhanced chemoradiation. These findings how co-option, plasticity jointly drive therapy during recurrence.

Language: Английский

Citations

7
Cooperative pro-tumorigenic adaptation to oncogenic RAS through epithelial-to-mesenchymal plasticity DOI Creative Commons
Hadrien De Blander, Laurie Tonon, Frédérique Fauvet

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(7)

Published: Feb. 14, 2024

In breast cancers, aberrant activation of the RAS/MAPK pathway is strongly associated with mesenchymal features and stemness traits, suggesting an interplay between this mitogenic signaling epithelial-to-mesenchymal plasticity (EMP). By using inducible models human mammary epithelial cells, we demonstrate herein that oncogenic RAS promotes ZEB1-dependent EMP, which necessary for malignant transformation. Notably, EMP triggered by secretion pro-inflammatory cytokines from neighboring RAS-activated senescent a prominent role IL-6 IL-1α. Our data contrast common view cellular senescence as tumor-suppressive mechanism process promoting late stages tumor progression in response to signals microenvironment. We highlighted here pro-tumorigenic cooperation leverages on oncogene-induced trigger reprogramming

Language: Английский

Citations

6