Platinum-induced upregulation of ITGA6 promotes chemoresistance and spreading in ovarian cancer DOI Creative Commons
Alice Gambelli, Anna Nespolo, Gian Luca Rampioni Vinciguerra

и другие.

EMBO Molecular Medicine, Год журнала: 2024, Номер 16(5), С. 1162 - 1192

Опубликована: Апрель 24, 2024

Platinum (PT)-resistant Epithelial Ovarian Cancer (EOC) grows as a metastatic disease, disseminating in the abdomen and pelvis. Very few options are available for PT-resistant EOC patients, little is known about how acquisition of PT-resistance mediates increased spreading capabilities EOC. Here, using isogenic cells, genetic pharmacological approaches, patient-derived models, we report that Integrin α6 (ITGA6) overexpressed by cells necessary to sustain ability adhesion-dependent PT-resistance. Using vitro showed PT induces positive loop that, stimulating ITGA6 transcription secretion, contributes formation pre-metastatic niche enabling disseminate. At molecular level, engagement regulates production availability insulin-like growth factors (IGFs), over-stimulating IGF1R pathway upregulating Snail expression. In data were recapitulated vivo models which targeting prevents dissemination improves PT-activity, supporting promising druggable target patients.

Язык: Английский

Angiogenic signaling pathways and anti-angiogenic therapy for cancer DOI Creative Commons

Zhenling Liu,

Huanhuan Chen,

Lili Zheng

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 11, 2023

Abstract Angiogenesis, the formation of new blood vessels, is a complex and dynamic process regulated by various pro- anti-angiogenic molecules, which plays crucial role in tumor growth, invasion, metastasis. With advances molecular cellular biology, biomolecules such as growth factors, chemokines, adhesion factors involved angiogenesis has gradually been elucidated. Targeted therapeutic research based on these molecules driven treatment to become promising strategy anti-tumor therapy. The most widely used agents include monoclonal antibodies tyrosine kinase inhibitors (TKIs) targeting vascular endothelial factor (VEGF) pathway. However, clinical benefit this modality still limited due several defects adverse events, acquired drug resistance, recurrence, lack validated biomarkers, impel further mechanisms angiogenesis, development multiple drugs combination therapy figure out how improve efficacy. Here, we broadly summarize signaling pathways discuss current challenges We also propose approaches efficacy provide perspective for

Язык: Английский

Процитировано

543
RGD peptide in cancer targeting: Benefits, challenges, solutions, and possible integrin–RGD interactions DOI Creative Commons
Hossein Javid, Mahsa Akbari Oryani,

Nastaran Rezagholinejad

и другие.

Cancer Medicine, Год журнала: 2024, Номер 13(2)

Опубликована: Янв. 1, 2024

RGD peptide can be found in cell adhesion and signaling proteins, such as fibronectin, vitronectin, fibrinogen. peptides' principal function is to facilitate by interacting with integrin receptors on the surface. They have been intensively researched for use biotechnology medicine, including incorporation into biomaterials, conjugation medicinal molecules or nanoparticles, labeling imaging agents. peptides utilized specifically target cancer cells tumor vasculature engaging these integrins, improving drug delivery efficiency minimizing adverse effects healthy tissues. RGD-functionalized carriers are a viable option therapy this focused approach has demonstrated promise future. Writing review significantly influence how drugs developed future our understanding of peptide, finding knowledge gaps, fostering innovation, making design easier.

Язык: Английский

Процитировано

62
Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition DOI Creative Commons
Antonino Glaviano,

Hannah Lau,

Lukas M. Carter

и другие.

Journal of Hematology & Oncology, Год журнала: 2025, Номер 18(1)

Опубликована: Янв. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Язык: Английский

Процитировано

19
The regulatory role of integrin in gastric cancer tumor microenvironment and drug resistance DOI
Songlin Wu, Abdel Nasser B. Singab,

Guimei LlN

и другие.

Progress in Biophysics and Molecular Biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

3
Regulation of tumor immunity and immunotherapy by the tumor collagen extracellular matrix DOI Creative Commons
Dallas B. Flies, Solomon Langermann, Christina Jensen

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Авг. 17, 2023

It has been known for decades that the tumor extracellular matrix (ECM) is dysfunctional leading to loss of tissue architecture and promotion growth. The altered ECM fibrogenesis leads stiffness act as a physical barrier immune cell infiltration into microenvironment (TME). becoming increasingly clear plays important roles in responses. A growing body data now indicates components also play more active role regulation when dysregulated ligands interact with receptors on cells inhibit subpopulations TME. In addition, immunotherapies such checkpoint inhibitors are approved treat cancer often hindered by changes. this review we highlight ways which alterations affect regulate immunity cancer. More specifically, how collagens major components, suppress complex Finally, will our increased understanding immunotherapy towards novel disruptive strategies overcome suppression.

Язык: Английский

Процитировано

32
Compressive stresses in cancer: characterization and implications for tumour progression and treatment DOI

Julia A Linke,

Lance L. Munn, Rakesh K. Jain

и другие.

Nature reviews. Cancer, Год журнала: 2024, Номер 24(11), С. 768 - 791

Опубликована: Окт. 10, 2024

Язык: Английский

Процитировано

12
The Role of αvβ3 Integrin in Cancer Therapy Resistance DOI Creative Commons
Bianca Cruz Pachane, Heloísa Sobreiro Selistre-de-Araújo

Biomedicines, Год журнала: 2024, Номер 12(6), С. 1163 - 1163

Опубликована: Май 24, 2024

A relevant challenge for the treatment of patients with neoplasia is development resistance to chemo-, immune-, and radiotherapies. Although causes therapy are poorly understood, evidence suggests it relies on compensatory mechanisms that cells develop replace specific intracellular signaling should be inactive after pharmacological inhibition. One such mechanism involves integrins, membrane receptors connect extracellular matrix have a crucial role in cell migration. The blockage one type integrin frequently compensated by overexpression another dimer, generally supporting adhesion In particular, αvβ3 key receptor involved tumor treatments tyrosine kinase inhibitors, immune checkpoint radiotherapy; however, inhibition not enough avoid relapse. Here, we review been proposed thus far. Despite our focus integrin, important note other integrins also implicated drug collaborative action between these neglected.

Язык: Английский

Процитировано

10
Role of RGD-binding Integrins in ovarian cancer progression, metastasis and response to therapy DOI
Vipin Ranga, Tikam Chand Dakal, Pawan Kumar Maurya

и другие.

Integrative Biology, Год журнала: 2025, Номер 17

Опубликована: Янв. 1, 2025

Integrins are transmembrane receptors that play a crucial role in cell adhesion and signaling by connecting the extracellular environment to intracellular cytoskeleton. After binding with specific ligands matrix (ECM), integrins undergo conformational changes transmit signals across membrane. The integrin-mediated bidirectional triggers various cellular responses, such as shape, migration proliferation. Irregular integrin expression activity closely linked tumor initiation, angiogenesis, motility, invasion, metastasis. Thus, understanding intricate regulatory mechanism is essential for slowing cancer progression preventing carcinogenesis. Among four classes of integrins, arginine-glycine-aspartic acid (RGD)-binding stand out most receptor subfamily its Dysregulation almost all RGD-binding promotes ECM degradation ovarian cancer, resulting carcinoma resistance therapy. Preclinical studies have demonstrated targeting these therapeutic antibodies ligands, RGD-containing peptides their derivatives, can enhance precision agents treating cancer. Therefore, development novel This review mainly discusses genes importance different subtypes, involvement RGD motif-containing proteins carcinoma, ongoing, completed, partially unsuccessful clinical trials agents, well existing limitations challenges, advancements made so far, potential strategies, directions future research field. Insight Box Integrin-mediated regulates migration, proliferation differentiation. Dysregulated promote growth dissemination. proper this complex delay prevent Notably, motifs an important evolution, small molecules motifs, target disrupt interactions ECM, thereby inhibiting migration. Altogether, highlights providing new insights into metastasis how been utilized develop effective treatment plans.

Язык: Английский

Процитировано

2
The role of the hypothalamic–pituitary–thyroid axis in thyroid cancer DOI
Laura Abaandou, Raisa Ghosh, Joanna Kłubo-Gwieździńska

и другие.

The Lancet Diabetes & Endocrinology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis DOI Creative Commons
Smitha Sammith Shetty, Kanaka Sai Ram Padam, Mohit Sharma

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 26, 2025

Abstract Oral submucous fibrosis (OSF) is a chronic, progressive, and fibrotic condition of the oral mucosa that carries an elevated risk malignant transformation. We aimed to identify validate novel genes associated with regulation epithelial-to-mesenchymal transition (EMT) in OSF. Genes regulating EMT were identified through differential gene expression analysis, using LogFC threshold -1 + 1 padj value < 0.05, based on data from GEO datasets TCGA-HNSC datasets. The curated correlated functional cancer states subjected clustering candidate genes. Integration bioinformatics proteomics led discovery MMP9 , SPARC ITGA5 as candidates. Comprehensive pathway immunohistochemical analyses confirmed their roles OSF, squamous cell carcinoma (OSCC), OSF-associated (OSFSCC). significant malignancy suggest mechanism which fibrosis-associated type 2 undergoes 3 EMT, driving OSF towards malignancy.

Язык: Английский

Процитировано

1