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

Lactic acid in tumor invasion DOI
Dun Niu, Ting Luo, Hanbin Wang

et al.

Clinica Chimica Acta, Journal Year: 2021, Volume and Issue: 522, P. 61 - 69

Published: Aug. 13, 2021

Language: Английский

Citations

41
Partial EMT in Squamous Cell Carcinoma: A Snapshot DOI Creative Commons
Chengcheng Liao, Qian Wang, Jiaxing An

et al.

International Journal of Biological Sciences, Journal Year: 2021, Volume and Issue: 17(12), P. 3036 - 3047

Published: Jan. 1, 2021

In the process of cancer EMT, some subgroups cells simultaneously exhibit both mesenchymal and epithelial characteristics, a phenomenon termed partial EMT (pEMT).pEMT is plastic state in which coexpress markers.In squamous cell carcinoma (SCC), pEMT regulated, phenotype maintained via HIPPO pathway, NOTCH pathway TGF-β pathways by microRNAs, lncRNAs microenvironment (CME); thus, SCC exhibits aggressive tumorigenic properties high stemness, leads collective migration therapy resistance.Few studies have reported therapeutic interventions to address that undergone pEMT, this approach may be an effective way inhibit plasticity, drug resistance metastatic potential SCC.

Language: Английский

Citations

40
Progress of tumor-associated macrophages in the epithelial-mesenchymal transition of tumor DOI Creative Commons
Xiaoxiao Li, Ling Chen, Xiaobo Peng

et al.

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: July 28, 2022

As a significant public health problem with high morbidity and mortality worldwide, tumor is one of the major diseases endangering human life. Moreover, metastasis most important contributor to death patients. Epithelial-mesenchymal transition (EMT) an essential biological process in developing primary tumors metastasis. It underlies progression by inducing series alterations cells that confer ability move migrate. Tumor-associated macrophages (TAMs) are infiltrating immune microenvironment, they play indispensable role EMT interacting cells. With increasing clarity relationship between TAMs metastasis, targeting processes emerging as promising target for new cancer therapies. Therefore, this paper reviews recent research progress tumor-associated epithelial-mesenchymal briefly discusses current anti-tumor therapies processes.

Language: Английский

Citations

27
Mechanisms of Cisplatin Resistance in HPV Negative Head and Neck Squamous Cell Carcinomas DOI Creative Commons

Ana Belén Griso,

Lucía Acero-Riaguas, Beatriz Castelo

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(3), P. 561 - 561

Published: Feb. 5, 2022

Head and neck squamous cell carcinomas (HNSCCs) are the eighth most common cancers worldwide. While promising new therapies emerging, cisplatin-based chemotherapy remains gold standard for advanced HNSCCs, although of patients relapse due to development resistance. This review aims condense different mechanisms involved in cisplatin resistance HNSCCs highlight future perspectives intended overcome its related complications. Classical include drug import export, DNA repair oxidative stress control. Emerging research identified prevalence these populations cancer stem cells (CSC), which mainly contributing The use old CSC markers has enabled identification characteristics within HNSCC CSCs predisposing them treatment resistance, such as quiescence, increased self-renewal capacity, low reactive oxygen species levels or acquisition epithelial mesenchymal transcriptional programs. In present review, we will discuss how intrinsic extrinsic cues alter phenotype they influence treatment. addition, assess stromal composition tumor microenvironment affect CSCs' through a complex interplay between extracellular matrix content well immune non-immune characteristics. Finally, describe alterations epigenetic modifiers other signaling pathways can behavior plasticity induce data generated recent years open up wide range strategies optimize therapy, with potential personalize patient strategies.

Language: Английский

Citations

26
Lung cancer cell-intrinsic IL-15 promotes cell migration and sensitizes murine lung tumors to anti-PD-L1 therapy DOI Creative Commons
Shaojie Hu,

Kelin Meng,

Tianlai Wang

et al.

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: April 19, 2024

Abstract Background IL-15 plays a vital role in enhancing NK cell- and T-cell-mediated antitumor immune responses; however, the direct effect of on tumor cells has not been fully elucidated. Herein, we investigated lung adenocarcinoma cells. Methods Silencing overexpression techniques were used to modify endogenous expression Transwell assays assess cell migration invasion; live-cell analysis system was evaluate motility; cellular morphological changes quantified by confocal fluorescence microscopy; molecular mechanisms underlying analyzed western blotting; RhoA Cdc42 activities evaluated pulldown assay. NCG C57BL/6 mouse models functions vivo. Results Cancer cell-intrinsic promoted motility vitro metastasis vivo via activation AKT-mTORC1 pathway; exogenous inhibited suppression RhoA-MLC2 axis. Mechanistic revealed that both intracellular extracellular IL-15-mediated effects required IL-15Rα Detailed analyses IL-2/IL-15Rβ IL-2Rγ chains undetected complex formed IL-15Rα. However, when engaged cells, containing IL-15Rα, IL-2/IL-15Rβ, formed, indicating differential actions might be caused their distinctive modes receptor engagement. Using Lewis carcinoma (LLC) model, showed although facilitated LLC IL-15-overexpressing tumors more sensitive anti-PD-L1 therapy than IL-15-wild-type an enhanced response, as evidenced increased CD8 + T-cell infiltration compared counterparts. Conclusions differentially regulate migration. Thus, cancer acts double-edged sword progression. Additionally, high levels expressed improve responsiveness immunotherapies.

Language: Английский

Citations

5
An integrative alginate-based 3D in vitro model to explore epithelial-stromal cell dynamics in the breast tumor microenvironment DOI Creative Commons
Patrícia Barros da Silva,

Raquel Oliveira,

M. Araújo

et al.

Carbohydrate Polymers, Journal Year: 2024, Volume and Issue: 342, P. 122363 - 122363

Published: June 5, 2024

The tumor microenvironment (TME) orchestrates cellular and extracellular matrix (ECM) interactions, playing a key role in tumorigenesis, growth, metastization. Investigating the interplay between stromal-epithelial cells within TME is paramount for understanding cancer mechanisms but demands reliable biological models. 3D-models have emerged as powerful vitro tools, many fall short replicating cell-cell/cell-matrix interactions. This study introduces novel hybrid 3D-model of breast TME, combining epithelial cells, cancer-associated fibroblasts (CAFs), their ECM. To build stromal compartment, porous 3D-printed alginate scaffolds were seeded with CAFs, which proliferated produced pores infused oxidized peptide-modified hydrogel laden MCF10A forming parenchymal compartment. system supported morphogenesis into acini surrounded by ECM, could be readily solubilized to recover matrix, sequestered soluble factors. Proteome profiling retrieved ECM showed upregulation proteins associated assembly/remodeling, epithelial-to-mesenchymal transition (EMT), cancer. TME-like induced partial EMT generating population mesenchymal features, characteristic aggressive phenotypes. Our model provided new insights epithelial-stromal interactions offering valuable tool research physiologically-relevant 3D setting.

Language: Английский

Citations

5
TGF-β generates a population of cancer cells residing in G1 phase with high motility and metastatic potential via KRTAP2-3 DOI Creative Commons
Kazuki Takahashi, Katarzyna A. Podyma‐Inoue, Maki Saito

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 40(13), P. 111411 - 111411

Published: Sept. 1, 2022

Transforming growth factor β (TGF-β) increases epithelial cancer cell migration and metastasis by inducing epithelial-mesenchymal transition (EMT). TGF-β also inhibits proliferation G1 phase cell-cycle arrest. However, the correlation between these tumor-promoting -suppressing effects remains unclear. Here, we show that confers higher motility metastatic ability to oral cells in phase. Mechanistically, keratin-associated protein 2-3 (KRTAP2-3) is a regulator of dual TGF-β, its expression correlated with tumor progression patients head neck migratory potentials cells. Furthermore, single-cell RNA sequencing reveals generates two populations mesenchymal differential status through distinctive EMT pathways mediated Slug/HMGA2 KRTAP2-3. Thus, TGF-β-induced KRTAP2-3 orchestrates EMT, suggesting motile arrested as target suppress metastasis.

Language: Английский

Citations

20
A specialist-generalist framework for epithelial-mesenchymal plasticity in cancer DOI
David P. Cook, Jeffrey L. Wrana

Trends in cancer, Journal Year: 2022, Volume and Issue: 8(5), P. 358 - 368

Published: Feb. 17, 2022

Language: Английский

Citations

19
PD-L1 Activity Is Associated with Partial EMT and Metabolic Reprogramming in Carcinomas DOI Creative Commons

Srinath Muralidharan,

Manas Sehgal,

Soundharya Ramu

et al.

Current Oncology, Journal Year: 2022, Volume and Issue: 29(11), P. 8285 - 8301

Published: Oct. 31, 2022

Immune evasion and metabolic reprogramming are hallmarks of cancer progression often associated with a poor prognosis frequently present significant challenges for therapies. Recent studies have highlighted the dynamic interaction between immunosuppression dysregulation energy metabolism in modulating tumor microenvironment to promote aggressiveness. However, pan-cancer association among these two hallmarks, potent common driver them—epithelial-mesenchymal transition (EMT)—remains be done. This meta-analysis across 184 publicly available transcriptomic datasets as well The Cancer Genome Atlas (TCGA) data reveals that an enhanced PD-L1 activity signature along other immune checkpoint markers correlate positively partial EMT elevated glycolysis but reduced OXPHOS many carcinomas. These trends were also recapitulated single-cell, RNA-seq, time-course induction cell lines. Furthermore, multiple types, concurrent enrichment results worse outcomes terms overall survival compared only or expression. highlight potential functional synergy interconnected axes cellular plasticity enabling metastasis multi-drug resistance cancer.

Language: Английский

Citations

19
Polo-like kinase 4 (Plk4) potentiates anoikis-resistance of p53KO mammary epithelial cells by inducing a hybrid EMT phenotype DOI Creative Commons
Irina Fonseca, Cíntia Horta, Ana Sofia Ribeiro

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(2)

Published: Feb. 16, 2023

Abstract Polo-like kinase 4 (Plk4), the major regulator of centriole biogenesis, has emerged as a putative therapeutic target in cancer due to its abnormal expression human carcinomas, leading centrosome number deregulation, mitotic defects and chromosomal instability. Moreover, Plk4 deregulation promotes tumor growth metastasis mouse models is significantly associated with poor patient prognosis. Here, we further investigate role carcinogenesis show that overexpression potentiates resistance cell death by anoikis nontumorigenic p53 knock-out (p53KO) mammary epithelial cells. Importantly, this effect independent Plk4’s suggesting additional cellular functions. Interestingly, Plk4-induced induction stable hybrid epithelial-mesenchymal phenotype partially dependent on P-cadherin upregulation. Furthermore, found conditioned media p53KO cells also induces breast paracrine way, being soluble secretion. Our work shows, for first time, high levels induce both background, well exposed their secretome, which mediated through These results reinforce idea Plk4, independently functions an oncogene, impacting microenvironment promote malignancy.

Language: Английский

Citations

12