YAP1 Inhibition Induces Phenotype Switching of Cancer-Associated Fibroblasts to Tumor Suppressive in Prostate Cancer DOI Creative Commons
Hongtao Song, Tong Lü, Donghui Han

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(22), P. 3728 - 3742

Published: Aug. 13, 2024

Prostate cancer rarely responds to immune-checkpoint blockade (ICB) therapies. Cancer-associated fibroblasts (CAF) are critical components of the immunologically "cold" tumor microenvironment and considered a promising target enhance immunotherapy response. In this study, we aimed reveal mechanisms regulating CAF plasticity identify potential strategies switch CAFs from protumorigenic antitumor phenotypes ICB efficacy in prostate cancer. Integration four single-cell RNA sequencing datasets defined CAFs, RNA-seq, flow cytometry, organoid model demonstrated functions two subtypes. Extracellular matrix-associated (ECM-CAF) promoted collagen deposition cell progression, lymphocyte-associated (Lym-CAF) exhibited an phenotype induced infiltration activation CD8+ T cells. YAP1 activity regulated ECM-CAF phenotype, silencing switching Lym-CAFs. NF-κB p65 was core transcription factor Lym-CAF subset, inhibited nuclear translocation p65. Selective depletion ECM-CAFs vivo T-cell enhanced therapeutic effects anti-PD-1 treatment on Overall, study revealed mechanism identity highlighted strategy for altering subtype suppress growth increase sensitivity ICB. Significance: regulates cancer-associated fibroblast can be targeted that promotes extracellular matrix tumor-suppressive stimulates immunity efficacy.

Language: Английский

Glycolysis reprogramming in CAFs promotes oxaliplatin resistance in pancreatic cancer through circABCC4 mediated PKM2 nuclear translocation DOI Creative Commons

Rihua He,

Chonghui Hu, Yuan Yuan

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 23, 2025

Language: Английский

Citations

3
Antigen-presenting cancer associated fibroblasts enhance antitumor immunity and predict immunotherapy response DOI Creative Commons
Junquan Song,

Rongyuan Wei,

Chenchen Liu

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 4, 2025

Cancer-associated fibroblasts (CAF) play a crucial role in tumor progression and immune regulation. However, the functional heterogeneity of CAFs remains unclear. Here, we identify antigen-presenting (apCAF), characterized by high MHC II expression, gastric cancer (GC) tumors find that apCAFs are preferentially located near tertiary lymphoid structures. Both vivo vitro experiments demonstrate promote T cell activation enhances its cytotoxic proliferative capacities, thereby strengthening cell-mediated anti-tumor immunity. Additionally, facilitate polarization macrophages toward pro-inflammatory phenotype. These polarized macrophages, turn, formation apCAFs, creating positive feedback loop amplifies responses. Notably, baseline immunotherapy responders across various types exhibit higher levels infiltration. This study advances understanding GC highlights as potential biomarker for predicting response pan-cancer.

Language: Английский

Citations

3
Cancer-associated fibroblast-derived extracellular vesicles: regulators and therapeutic targets in the tumor microenvironment DOI Open Access
Jindong Xie, Xinmei Lin, Xinpei Deng

et al.

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Cancer-associated fibroblasts (CAFs) constitute a critical component of the tumor microenvironment (TME). CAFs can be reprogrammed by cancer cells, leading to production extracellular vesicles (EVs). These EVs serve as carriers for bioactive substances, including proteins, nucleic acids, and metabolic products, thereby facilitating progression. CAF-derived exert substantial influence on cell proliferation, invasion, metastasis, immunological environment, processes lymphangiogenesis angiogenesis. Despite their potential non-invasive biomarkers therapeutic delivery vehicles, clinical application is currently limited challenges in purification precise targeting. This review delineates diverse roles growth, immune evasion within TME.

Language: Английский

Citations

2
Single-cell Transcriptomics Reveals Intratumor Heterogeneity and the Potential Roles of Cancer Stem Cells and myCAFs in Colorectal Cancer Liver Metastasis and Recurrence DOI Creative Commons

Zhan Yao,

Dong Sun, Jie Gao

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217452 - 217452

Published: Jan. 1, 2025

Language: Английский

Citations

2
GRP78 as a potential therapeutic target in cancer treatment: an updated review of its role in chemoradiotherapy resistance of cancer cells DOI Creative Commons
Min Lin, Yan Mo, Chengmin Li

et al.

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(2)

Published: Jan. 18, 2025

Language: Английский

Citations

2
Deciphering mechanical cues in the microenvironment: from non-malignant settings to tumor progression DOI Creative Commons
Yi‐Cheng Zhu,

Jiaoshun Chen,

Chen Chen

et al.

Biomarker Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 23, 2025

The tumor microenvironment functions as a dynamic and intricate ecosystem, comprising diverse array of cellular non-cellular components that precisely orchestrate pivotal behaviors, including invasion, metastasis, drug resistance. While unraveling the interplay between behaviors represents tremendous challenge, recent research illuminates crucial biological phenomenon known mechanotransduction. Within microenvironment, mechanical cues like tensile stress, shear stiffness play role by activating mechanosensitive effectors such PIEZO proteins, integrins, Yes-associated protein. This activation initiates cascades intrinsic signaling pathways, effectively linking physical properties tissues to their physiological pathophysiological processes morphogenesis, regeneration, immunity. mechanistic insight offers novel perspective on how within impact behaviors. intricacies are yet be fully elucidated, it exhibits distinct attributes from non-malignant tissues, elevated solid stresses, interstitial hypertension, augmented matrix stiffness, enhanced viscoelasticity. These traits exert notable influences progression treatment responses, enriching our comprehension multifaceted nature microenvironment. Through this innovative review, we aim provide new lens decipher contexts, broadening knowledge these factors promote or inhibit thus offering valuable insights identify potential targets for anti-tumor strategies.

Language: Английский

Citations

2
Tumor-derived exosomal KPNA2 activates fibroblasts and interacts with KIFC1 to promote bladder cancer progression, a process inhibited by miR-26b-5p DOI Creative Commons
Cong Yin, Cen Liufu, Shuai Ye

et al.

Cellular & Molecular Biology Letters, Journal Year: 2025, Volume and Issue: 30(1)

Published: Feb. 16, 2025

Abstract Background Recent studies have illuminated the complexities of treating advanced bladder cancer (BCa), underscoring importance comprehending its molecular mechanisms for creating novel therapies. While role Karyopherin a2 ( KPNA2 ) in promoting BCa growth is established, precise mechanism remains elusive. Methods To investigate regulatory BCa, we employed a comprehensive approach integrating clinical case data and bioinformatics analysis to evaluate expression tissues. Mechanisms by were examined using both vivo vitro models. Results Our research reveals that miR-26b-5p acts as an anticancer factor targeting inhibiting expression. Furthermore, observed interaction between Kinesin Family Member C1 KIFC1 facilitates transition cells into G2/M phase, thereby tumor advancement via activation Phosphoinositide 3-kinase (PI3K)- Protein Kinase B (AKT) pathway. Importantly, this investigation first identify exosomes originating from Plasma patients with exhibited notably increased levels compared healthy controls, suggesting potential new indicator. Additionally, triggered conversion fibroblasts cancer-associated (CAFs), which secreted elevated interleukin-6 (IL-6), contributing tumor-supporting environment. Conclusions These findings suggest key gene promotes progression, can potentially be marker, may serve therapeutic target BCa. Graphical

Language: Английский

Citations

2
Extracellular vesicle-circEHD2 promotes the progression of renal cell carcinoma by activating cancer-associated fibroblasts DOI Creative Commons
Tao He, Qiansheng Zhang, Peng Xu

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: July 22, 2023

Abstract Background The encapsulation of circular RNAs (circRNAs) into extracellular vesicles (EVs) enables their involvement in intercellular communication and exerts an influence on the malignant advancement various tumors. However, regulatory role EVs-circRNA renal cell carcinoma (RCC) remains elusive. Methods vitro vivo functional experiments were implemented to measure effects circEHD2 phenotype RCC. EVs-circEHD2 activation fibroblasts was assessed by collagen contraction assay, western blotting, enzyme-linked immunosorbent assay (ELISA). mechanism investigated RNA pull-down immunoprecipitation, chromatin isolation purification, luciferase co-immunoprecipitation assay. Results We demonstrated that upregulated RCC tissues serum EVs patients with metastasis. Silencing inhibited tumor growth vivo. Mechanistic studies indicated FUS -binding protein (FUS) accelerated cyclization circEHD2, then interacts tyrosine 3-monooxygenase/tryptophan 5-monooxygenase eta (YWHAH), which acts as a bridge recruit Yes1-associated transcriptional regulator (YAP) promoter SRY-box transcription factor 9 (SOX9); this results sustained SOX9. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) regulates package EVs, transmits fibroblasts, converting cancer-associated (CAFs). Activated CAFs promote metastasis secreting pro-inflammatory cytokines such IL-6. Furthermore, antisense oligonucleotides (ASOs) targeting exhibited strong inhibition Conclusions circEHD2/YWHAH/YAP/SOX9 signaling pathway accelerates facilitates CAFs. Our suggest may be useful biomarker therapeutic target for

Language: Английский

Citations

29
Functionally distinct cancer-associated fibroblast subpopulations establish a tumor promoting environment in squamous cell carcinoma DOI Creative Commons
Sabrina Schütz, Llorenç Solé‐Boldo,

Carlota Lucena-Porcel

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 5, 2023

Abstract Cutaneous squamous cell carcinoma (cSCC) is a serious public health problem due to its high incidence and metastatic potential. It may progress from actinic keratosis (AK), precancerous lesion, or the in situ carcinoma, Bowen’s disease (BD). During this progression, malignant keratinocytes activate dermal fibroblasts into tumor promoting cancer-associated (CAFs), whose origin emergence remain largely unknown. Here, we generate analyze >115,000 single-cell transcriptomes healthy skin, BD cSCC of male donors. Our results reveal immunoregulatory matrix-remodeling CAF subtypes that derive pro-inflammatory mesenchymal fibroblasts, respectively. These are absent AK interact with different types establish pro-tumorigenic microenvironment. findings cSCC-specific could not be recapitulated basal carcinomas. study provides important insights potential functionalities CAFs will highly beneficial for specific targeting

Language: Английский

Citations

26
Cancer-Associated Fibroblast Heterogeneity and Its Influence on the Extracellular Matrix and the Tumor Microenvironment DOI Open Access
Karl Knipper, Su Ir Lyu, Alexander Quaas

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13482 - 13482

Published: Aug. 30, 2023

The tumor microenvironment comprises multiple cell types, like cancer cells, endothelial fibroblasts, and immune cells. In recent years, there have been massive research efforts focusing not only on but also other types of the microenvironment, thereby aiming to expand determine novel treatment options. Fibroblasts represent a heterogenous family consisting numerous subtypes, which can alter fractions, facilitate or inhibit growth, build pre-metastatic niches, stabilize vessels. These effects be achieved through cell–cell interactions, form extracellular matrix, via secretion cytokines chemokines. pro- antitumorigenic fibroblast phenotypes show variability among different entities, intraindividual sites, including primary tumors metastatic lesions. Commonly prescribed for arterial hypertension, inhibitors renin–angiotensin system recently described as having an inhibitory effect fibroblasts. This inhibition leads modified fractions increased tissue stiffness, contributing overcoming therapy resistance ultimately inhibiting growth. However, it is important note that fibroblasts opposite effect, potentially resulting in We aim summarize latest state regarding heterogeneity its intricate impact matrix. Specifically, we focus highlighting advancements comprehension options within this context.

Language: Английский

Citations

24