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Development of a novel and economical agar-based non-adherent three-dimensional culture method for enrichment of cancer stem-like cells.

BACKGROUND: Non-adherent or ultra-low attachment three-dimensional (3D) culture, also called sphere formation assay, has been widely used to assess the malignant phenotype and stemness potential of transformed or cancer cells. This method is also popularly used to isolate the cancer stem-like cells (CSCs) or tumor-initiating cells based on their unique anchorage-independent growth or anoikis-resistant capacity. Different non-adhesive coating agents, such as poly-2-hydroxyethyl methacrylate (poly-HEMA) and synthetic hydrogels, have been used in this non-adherent 3D culture. However, preparation…

Integrated transcriptomic profiling of programmed cell death patterns unveils macrophage-hepatocyte crosstalk via THBS1-CD47 axis in hepatic ischemia-reperfusion injury.

BACKGROUND: Hepatic ischemia-reperfusion injury (HIRI) is clinically linked to post-transplant complications, yet the pathogenic role of pro … ed elevated expression in high-risk groups, accompanied by pronounced enrichment of 5 PCD patterns (anoikis, immunogenic cell death, NETosis, Netotic cell death, pyroptosis). Single-cell analysis further uncovered 12 distinct PCD patterns within the HIRI sample microenvironment, with spatial validation confirming the 5 hub DE-PCDRGs. The HIRI animal model …

Genomic and clinical characterization of HER2 exon 20 mutations in non-small cell lung cancer: insights from a multicenter study in South China.

BACKGROUND: The objective of this study was to investigate the clinical and genetic characteristics and clinical relevance of HER2 exon 20 o … %). Gene Ontology (GO) analysis linked exon 20 mutations to unregulated protein kinase activity and anoikis. CONCLUSIONS: Our study found that NSCLC patients with HER2 exon 20 oncogenic variants have a higher risk of metastasis and drug resistance, leading to worse outcomes than non-exon 20 mutations. This highlights the urgent need for targeted therapie …

Using an in-vivo syngeneic spontaneous metastasis model identifies ID2 as a promoter of breast cancer colonisation in the brain.

BACKGROUND: Dissemination of breast cancers to the brain is associated with poor patient outcome and limited therapeutic options. In this st … ate that either ectopic expression of ID2 or BMP7-induced ID2 expression protects tumour cells from anoikis. CONCLUSIONS: This study identifies ID2 as a key regulator of breast cancer metastasis to the brain. Our data support a model in which breast cancer cells that have disseminated to the brain upregulate ID2 expression in response to astrocyte-secret …

Hepatocellular carcinoma hosts cholinergic neural cells and tumoral hepatocytes harboring targetable muscarinic receptors.

BACKGROUND & AIMS: Owing to unexplained interpatient variation and treatment failure in hepatocellular carcinoma (HCC), novel therapeutic ap … tions of anticholinergic drugs, but not cholinomimetics, decreased anchorage-independent growth and anoikis, synergized with sorafenib and lenvatinib in HCC class 1 to 3 lines, yet not in primary human hepatocytes, and preserved mature hepatocyte functions. CONCLUSION: These data identify cholinergic processes as instrumental in liver carcinogenesis and …

Deficiency of epithelial-mesenchymal transition causes child indirect inguinal hernia.

INTRODUCTION: Epithelial-mesenchymal transition (EMT) describes rapid changes in cellular phenotype. During EMT, epithelial cells down-modulate cell-cell adhesion, alter polarity, reorganize cytoskeleton, become isolated, motile, and resistant to anoikis. Epithelial breakdown and epithelial cell migration are the key processes involved in the obliteration of processus vaginalis. The great majority of abnormalities are because of nonobliteration or incomplete fusion of PV. We aimed to analyze the quantitative changes of epithelial genes in adult/child patients and their controls to examine diff…

Apoptosis is not required for acantholysis in pemphigus vulgaris.

The autoimmune blistering skin disease pemphigus vulgaris (PV) is caused primarily by autoantibodies against desmosomal cadherins. It was reported that apoptosis can be detected in pemphigus skin lesions and that apoptosis can be induced by PV-IgG in cultured keratinocytes. However, the role of apoptosis in PV pathogenesis is unclear at present. In this study, we provide evidence that apoptosis is not required for acantholysis in PV. In skin lesions from two PV patients, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positivity, but not cleaved caspase-3, was det

The characterization and validation of regulated cell death-related genes in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Regulated cell death (RCD), a genetically controlled process mediated by specialized molecular pathways (commonly termed program … ecroptosis, entotic cell death, lysosome-dependent cell death, NETosis, immunogenic cell death, and anoikis. Pathway enrichment analysis demonstrated that RCD-related differentially expressed genes were predominantly involved in epithelial-mesenchymal transition (EMT) and immune-inflammatory regulation. Furthermore, the WGCNA algorithm and LASSO analysis …

BAX activation in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct steps.

BACKGROUND: Pro-apoptotic BAX is a central mediator of retinal ganglion cell (RGC) death after optic nerve damage. BAX activation occurs in … , RGCs exhibited a significant delay between these two stages, similar to detached cells undergoing anoikis. Translocation, with minimal permeabilization could be induced in a subset of RGCs using an inhibitor of Focal Adhesion Kinase (PF573228). Permeabilization after ONC, in a majority of RGCs, could be inhibited with a broad spectrum kinase inhibitor ( …

BAX activation in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct steps.

Background Pro-apoptotic BAX is a central mediator of retinal ganglion cell (RGC) death after optic nerve damage. BAX activation occurs in t … , RGCs exhibited a significant delay between these two stages, similar to detached cells undergoing anoikis. Translocation, with minimal permeabilization could be induced in a subset of RGCs using an inhibitor of Focal Adhesion Kinase (PF573228). Permeabilization after ONC, in a majority of RGCs, could be inhibited with a broad spectrum kinase inhibitor ( …

Differential effects of anti-TNF-alpha drugs on fibroblast-like synoviocyte apoptosis.

OBJECTIVE: Novel drugs targeting TNF-alpha are available for treatment of RA. Fibroblast-like synoviocytes (FLSs) play a fundamental role in RA progression, through their expansion caused in part by resistance to cell death induction. The aim of our study was to determine the effects of different anti-TNF-alpha agents on FLS apoptosis. METHODS: FLS from patients with either RA or OA were co-cultured with peripheral blood mononuclear cells (PBMCs), and incubated with various drugs for 6 days. Subsequently, apoptosis induction was detected by Nucleosome ELISA and terminal deoxynucleotidyl trans

Identification of sex-specific biomarkers related to programmed cell death and analysis of immune cells in ankylosing spondylitis.

Ankylosing spondylitis (AS) stands as a persistent inflammatory ailment predominantly impacting the axial skeleton, with the immune system a … ocus extended specifically to ferroptosis-related DEGs (FRDEGs), cuproptosis-related DEGs (CRDEGs), anoikis-related DEGs (ARDEGs), autophagy-related DEGs (AURDEGs), and pyroptosis-related DEGs (PRDEGs). Further scrutiny involved discerning disparities in these DEGs between AS patients and healthy controls, as well as disparities between male and female pa …

Growth factor progranulin promotes tumorigenesis of cervical cancer via PI3K/Akt/mTOR signaling pathway.

Progranulin (PGRN) is an autocrine growth factor with tumorigenic roles in various tumors including cervical cancer. In this study, we investigated mammalian target of rapamycin (mTOR) signaling in response to PGRN induction and the contribution of the PGRN-stimulated PI3K/Akt/mTOR signaling pathway in the transformation and progression of cervical cancer. Here we identified a strong linkage between PGRN and phosphorylated-mTOR in cervical cancer tissues. PGRN promoted the phosphorylation of mTOR and activated mTOR signaling in human cervical mucosa epithelial cells and cervical cancer cells,

Emerging evidence of the molecular landscape specific for hematogenous metastasis from gastric cancer.

Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Most GC patients are diagnosed when the cancer is in an advanced stage, and consequently, some develop metastatic lesions that generally cause cancer-related death. Metastasis establishment is affected by various conditions, such as tumor location, hemodynamics and organotropism. While digestive cancers may share a primary site, certain cases develop hematogenous metastasis with the absence of peritoneal metastasis, and vice versa. Numerous studies have revealed the clinicopathological risk factors for hematogeno

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… Anoikis resistance is an important factor for metastasizing to distant organs in various cancers[ 30 ]. In GC, anoikis resistance has been relatively well investigated in peritoneal metastasis, which is the most frequent metastasis from GC[ 31 , 32 ]. … Although the mouse xenografts in their study were ectopic subcutaneous tumors, the results suggested that EGFL7 should play a pivotal role in the establishment of hematogenous metastasis via anoikis resistance. …

Molecular Pathogenesis and Diagnostic Imaging of Metastatic Jaw Tumors.

Metastasis is the spread of malignant cells from a primary tumor to distant sites through lymphatics or blood vessels. Malignant lesions metastasizing to the oral and perioral region are a rarity indeed. Malignant lesions could metastasize to both soft tissue of oral cavity and the hard tissues of the jaws and recent meta-analysis showed that metastasis is more common in the jaws than oral soft tissues because of rich vascular supply. The incidence is very low when compared to the incidence of primary oral cancers; nevertheless, one has to include in the diagnostic workup, metastatic malignant

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… When tumor cells enter unfamiliar environments, anoikis could obstruct metastasis by inducing apoptosis. … Anoikis and metastatic potential of cloudman S91 melanoma cells. Cancer Res. 2001;61:1707–16. 41. Liotta LA, Kohn E. Anoikis: Cancer and the homeless cell. Nature. 2004;430:973–4. doi: 10.1038/430973a. 42. Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D, et al. …

Microenvironmental Influences on Metastasis Suppressor Expression and Function during a Metastatic Cell's Journey.

Metastasis is the process of primary tumor cells breaking away and colonizing distant secondary sites. In order for a tumor cell growing in … atogenous) or lymphatic systems or travel across body cavities. In transit, tumor cells must resist anoikis, survive sheer forces and evade detection by the immune system. For blood-borne metastases, surviving cells then arrest or adhere to endothelial linings before either proliferating or extravasating. Eventually, tumor cells complete the process by pr …

Chronic stress in solid tumor development: from mechanisms to interventions.

Chronic stress results in disturbances of body hormones through the neuroendocrine system. Cancer patients often experience recurrent anxiety and restlessness during disease progression and treatment, which aggravates disease progression and hinders treatment effects. Recent studies have shown that chronic stress-regulated neuroendocrine systems secret hormones to activate many signaling pathways related to tumor development in tumor cells. The activated neuroendocrine system acts not only on tumor cells but also modulates the survival and metabolic changes of surrounding non-cancerous cells.

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… Anti-anoikis is a marker of malignant transformation. In addition to increasing cancer cell survival in the absence of stromal attachment, anti-anoikis promotes migration, re-attachment, and secondary sites colonization [ 63 ]. … Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis. J Clin Invest. 2010;120(5):1515–1523. doi: 10.1172/JCI40802. 55. …

New Directions in the Study and Treatment of Metastatic Cancer.

Traditional cancer therapy has relied on a strictly cytotoxic approach that views non-metastatic and metastatic tumor cells as identical in terms of molecular biology and sensitivity to therapeutic intervention. Mounting evidence suggests that, in fact, non-metastatic and metastatic tumor cells differ in key characteristics that could explain the capacity of the metastatic cells to not only escape the primary organ but also to survive while in the circulation and to colonize a distant organ. Here, we lay out a framework for a new multi-pronged therapeutic approach. This approach involves modif

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… One unique property of metastatic tumor cells that could be targeted for therapy is their resistance to anoikis. Anoikis is a type of programmed cell death, which occurs when anchorage-dependent cells detach from the ECM. … When these cells are detached from the ECM, they invariably undergo anoikis. By contrast, metastatic tumor cells can become resistant to anoikis. …

Current concepts in bone metastasis, contemporary therapeutic strategies and ongoing clinical trials.

BackgroundElucidation of mechanisms regulating bone metastasis has progressed significantly in recent years and this has translated to many new therapeutic options for patients with bone metastatic cancers. However, the rapid rate of progress in both the basic science literature and therapies undergoing clinical trials makes staying abreast with current developments challenging. This review seeks to provide an update on the current state of the science in bone metastasis research and give a snap shot of therapies in clinical trials for bone metastatic cancer.Main bodyBone metastasis represents

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… One specific example that has been linked to anoikis resistance is a tyrosine kinase receptor, TrkB. … Anoikis molecular pathways and its role in cancer progression. Biochim Biophys Acta. 2013;1833:3481–3498. doi: 10.1016/j.bbamcr.2013.06.026. 15. Douma S, et al. Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. …