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Influence of Fibroblasts on Mammary Gland Development, Breast Cancer Microenvironment Remodeling, and Cancer Cell Dissemination.

The stromal microenvironment regulates mammary gland development and tumorigenesis. In normal mammary glands, the stromal microenvironment encompasses the ducts and contains fibroblasts, the main regulators of branching morphogenesis. Understanding the way fibroblast signaling pathways regulate mammary gland development may offer insights into the mechanisms of breast cancer (BC) biology. In fact, the unregulated mammary fibroblast signaling pathways, associated with alterations in extracellular matrix (ECM) remodeling and branching morphogenesis, drive breast cancer microenvironment (BCM) rem

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… The coexpression of LN332 and integrin β4 elicits myofibroblast resistance to anoikis. Therefore, the anoikis resistant phenotype makes myofibroblasts, localized to the interface zone, the principal cells implicated in tissue remodeling during BC cell invasion [ 137 ]. …

ACY‑1215, a HDAC6 inhibitor, decreases the dexamethasone‑induced suppression of osteogenesis in MC3T3‑E1 cells.

Glucocorticoid‑induced osteoporosis is the commonest form of drug‑induced osteoporosis. Histone deacetylase 6 (HDAC6) is involved in the differentiation from mesenchymal stem cells to osteoblasts. However, the role of ricolinostat (ACY‑1215, HDAC6 inhibitor) in the dexamethasone (Dex)‑induced proliferation and differentiation of preosteoblasts remains to be elucidated. The protein expression and mRNA expression levels of HDAC6, osteopontin (OPN), runt‑related transcription factor 2 (Runx2), osterix (Osx), collagen I (COL1A1) and glucocorticoid receptor (GR) in MC3T3‑E1 cells were analyzed by w

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… Evidence for inside-out signaling leading to anoikis J Biol Chem 282 24120 24130 2007 10.1074/jbc.M611435200 17581824 30 Rauch A Seitz S Baschant U Schilling AF Illing A Stride B Kirilov M Mandic V Takacz A schmidt-ullrich R Glucocorticoids suppress bone formation by attenuating osteoblast differentiation …

Inflammatory Manifestations, Therapeutic Interventions, and Cancer Risk in Psoriasis: Current Epidemiological and Mechanistic Evidence.

Psoriasis is a chronic, autoimmune skin disease driven by persistent inflammation and immune dysfunction that severely impairs quality of life and is associated with serious comorbidities, including psoriatic arthritis, cardiovascular diseases (CVDs), and depression. Emerging epidemiological evidence suggests an association between psoriasis and an increased risk of certain malignancies, such as breast cancer (BC) and non-Hodgkin's lymphoma (NHL), although the strength and consistency of these associations vary across study designs, and the underlying thrombo-inflammatory mechanisms remain inc

Keyword Index for Volume 108

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… 1092 alternative splicing 2291 AMD11070 1634 AMG 386 503 AMPK 327 anaemia 387 anal cancer 527 anastrazole 2259 androgen deprivation 9 androgen receptor 139, 1668 angiogenesis 1126, 2123, 2485 angiogenesis inhibitors 1034 angiopoietin inhibitor 503 animal model 2312 animal studies 64 anoikis …

Mechanisms, Diagnosis and Treatment of Bone Metastases.

Bone and bone marrow are among the most frequent metastatic sites of cancer. The occurrence of bone metastasis is frequently associated with a dismal disease outcome. The prevention and therapy of bone metastases is a priority in the treatment of cancer patients. However, current therapeutic options for patients with bone metastatic disease are limited in efficacy and associated with increased morbidity. Therefore, most current therapies are mainly palliative in nature. A better understanding of the underlying molecular pathways of the bone metastatic process is warranted to develop novel, wel

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… Disseminated osteosarcoma cells can resist anoikis (detachment-induced cell death) by expressing fatty acid synthase and potentially related molecules including p-ERK1/2 and BCL-xL [ 154 ]. … Upon entering the circulation, Ewing sarcoma cells overcome anoikis by upregulating IL-1 receptor accessory protein (IL1RAP) enabling metastatic spread [ 180 ]. …

Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications.

The tumor microenvironment (TME) has been extensively investigated; however, it is complex and remains unclear, especially in elderly patients. Senescence is a cellular response to a variety of stress signals, which is characterized by stable arrest of the cell cycle and major changes in cell morphology and physiology. To the best of our knowledge, senescence leads to consistent arrest of tumor cells and remodeling of the tumor-immune microenvironment (TIME) by activating a set of pleiotropic cytokines, chemokines, growth factors, and proteinases, which constitute the senescence-associated sec

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… The activation of IGF-1R leads to the activation of PI3K, Ras-Raf, JAK/STAT3, and other pathways, ultimately upregulating p21, which promotes cell proliferation, survival, migration, and adaptation to hypoxia and inhibits autophagy, apoptosis, and anoikis [ 205 ]. … Circulating tumor cells (CTCs) originating from a primary focal point may die rapidly after entering the blood due to the shear force of the blood flow and anoikis [ 240 , 241 ]. …

The role of interleukin-17 in inflammation-related cancers.

Emerging evidence indicates a correlation between inflammation and the development and progression of cancer. Among the various inflammatory signals, interleukin-17 (IL-17) family cytokines serve as a critical link between inflammation and cancer. IL-17 is a highly versatile pro-inflammatory cytokine that plays a pivotal role in host defense, tissue repair, the pathogenesis of inflammatory diseases, and cancer progression. During the early stages of tumorigenesis, IL-17 signaling directly promotes the proliferation of tumor cells. Conversely, IL-17 has been shown to exhibit antitumor immunity

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… . | ( 111 ) BC | IL-17A | Human TNBC cell lines: MDA-MB-231/468 cell; In situ model with 4T1 in Il17 -/- immunodeficient NU-Foxn1nu mice | Pro-tumor | Directly promote the migration and angiogenic activity of breast cancer tumor cells and enhance anoikis resistance. | ( 112 ) Spontaneous metastasis model … It has also been shown that IL-17A can directly promote the migration and angiogenic activity of breast cancer tumor cells and enhance anoikis resistance ( 112 ). IL-17 signaling can stimulate systemic G-CSF, increasing neutrophil polarization, and promoting breast cancer metastasis ( 31 ). …

Amino acid metabolism in primary bone sarcomas.

Primary bone sarcomas, including osteosarcoma (OS) and Ewing sarcoma (ES), are aggressive tumors with peak incidence in childhood and adolescence. The intense standard treatment for these patients consists of combined surgery and/or radiation and maximal doses of chemotherapy; a regimen that has not seen improvement in decades. Like other tumor types, ES and OS are characterized by dysregulated cellular metabolism and a rewiring of metabolic pathways to support the biosynthetic demands of malignant growth. Not only are cancer cells characterized by Warburg metabolism, or aerobic glycolysis, bu

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… IL1RAP was found to be highly expressed in ES and important for promoting resistance to anoikis , detachment-induced cell death, and metastasis ( 99 ). … Proteomic screens for suppressors of anoikis identify IL1RAP as a promising surface target in Ewing sarcoma. Cancer Discovery (2021) 11(11):2884–903. doi: 10.1158/2159-8290.CD-20-1690 100. Mecham JO, Rowitch D, Wallace CD, Stern PH, Hoffman RM. …

The genetic architecture of bone metastases: unveiling the role of epigenetic and genetic modifications in drug resistance.

Bone metastases represent frequent and severe complications in various cancers, notably impacting prognosis and quality of life. This review article delves into the genetic and epigenetic mechanisms underpinning drug resistance in bone metastases, a key challenge in effective cancer treatment. The development of drug resistance in cancer can manifest as either intrinsic or acquired, with genetic heterogeneity playing a pivotal role. Intrinsic resistance is often due to pre-existing mutations, while acquired resistance evolves through genetic and epigenetic alterations during treatment. These a

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… The aggregation of migratory cancer cells enveloped in platelets and metabolic reprogramming confer resistance to mechanical injury, innate immune response, anoikis, and oxidative stress in the bloodstream [ 138 - 140 ] . … Platelets reduce anoikis and promote metastasis by activating YAP1 signaling. Nat Commun. 2017;8:310. doi: 10.1038/s41467-017-00411-z. 139. Mason JA, Hagel KR, Hawk MA, Schafer ZT. Metabolism during ECM detachment: achilles heel of cancer cells? …

Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients.

Osteosarcoma (OS) is a type of bone cancer that is derived from primitive mesenchymal cells typically affecting children and young adults. The current standard of treatment is a combination of neoadjuvant chemotherapy and surgical resection of the cancerous bone. Post-resection challenges in bone regeneration arise. To determine the appropriate amount of bone to be removed, preoperative imaging techniques such as bone and CT scans are employed. To prevent local recurrence, the current standard of care suggests maintaining bony and soft tissue margins from 3 to 7 cm beyond the tumor. The amount

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… Also, MSC-CM treatment increases the anoikis resistance of Saos2 cells in vitro, whereas exogenous MSC-CM promote the survival and metastasis of Saos2 cells in nude mice [ 124 ]. … CXCR1/Akt signaling activation induced by mesenchymal stem cell-derived IL-8 promotes osteosarcoma cell anoikis resistance and pulmonary metastasis. Cell Death Dis. 2018;9:714. doi: 10.1038/s41419-018-0745-0. Associated Data Data Availability Statement Not applicable. …

Keyword Index for Volume 110

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… 1269 alpha-fetoprotein 2277 amino-acid transporter 2030 amoeboid phenotype 2099 amphiregulin 648 amplification 2914 androgen receptor gene amplification 1655 aneuploidy 2159 angiogenesis 26, 107, 115, 469, 741, 946, 1027, 1034, 1179, 1269, 2700 angiogenic cytokines 441 animal welfare 928 anoikis …

Resveratrol downregulates interleukin-6-stimulated sonic hedgehog signaling in human acute myeloid leukemia.

IL-6 and sonic hedgehog (Shh) signaling molecules are considered to maintain the growth of cancer stem cells (CSCs). Resveratrol, an important integrant in traditional Chinese medicine, possesses certain antitumor effects. However, the mechanisms on regulating acute myeloid leukemia (AML) are unclear. This study first used human subjects to demonstrate that the plasma levels of IL-6 and IL-1 β in AML patients were higher and lower, respectively, than healthy donors. The expression of Shh preproproteins, and C- and N-terminal Shh peptides increased in bone marrow and peripheral blood mononuclea

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… Chu X Wei M Yang X Effects of an anthraquinone derivative from Rheum officinale Baill, emodin, on airway responses in a murine model of asthma Food and Chemical Toxicology 2012 50 7 2368 2375 22484343 10.1016/j.fct.2012.03.076 33 Hu B An HM Shen KP Song HY Deng S Polygonum cuspidatum extract induces anoikis …

CD13 downregulation mediated by ubenimex inhibits autophagy to overcome 5-FU resistance by disturbing the EMP3/FAK/NF-κB pathway in gastric cancer cells.

BackgroundGastric cancer (GC) is one of the most common malignant tumours in China, but the efficacy of chemotherapy on GC is significantly reduced due to the occurrence of drug resistance. Some studies have shown that the expression level of CD13 is associated with tumour resistance, but whether ubenimex, as a CD13 inhibitor, reverses GC drug resistance and the underlying mechanism remain unclear.MethodsHerein, resistance to 5-fluorouracil (5-FU) was reversed in GC by ubenimex, and the underlying mechanism was determined using Cell Counting Kit-8 (CCK-8) assays, gene chip analysis, high conte

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… Studies have shown that autophagy mediates tumour escape from anoikis and promotes tumour cell survival; therefore, cell autophagy induces the development of drug resistance in GC, which is closely related to its triggering of apoptosis tolerance ( 8 , 9 ). …

Blood Vessels and Peripheral Nerves as Key Players in Cancer Progression and Therapy Resistance.

Cancer cells continuously interact with the tumor microenvironment (TME), a heterogeneous milieu that surrounds the tumor mass and impinges on its phenotype. Among the components of the TME, blood vessels and peripheral nerves have been extensively studied in recent years for their prominent role in tumor development from tumor initiation. Cancer cells were shown to actively promote their own vascularization and innervation through the processes of angiogenesis and axonogenesis. Indeed, sprouting vessels and axons deliver several factors needed by cancer cells to survive and proliferate, inclu

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… Ultimately, OC cells exposed to either norepinephrine or epinephrine display enhanced proliferation and reduced sensitivity to anoikis: these effects are mediated by the focal adhesion kinase (FAK) signaling, and, indeed, OC patients with increased levels of FAK display a significantly worse overall … Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis. J. Clin. Investig. 2010;120:1515–1523. doi: 10.1172/JCI40802. 154. …

Exploring The Role of TOP2A in the Intersection of Pathogenic Mechanisms Between Rheumatoid Arthritis and Idiopathic Pulmonary Fibrosis Based on Bioinformatics.

BackgroundRheumatoid arthritis (RA) and idiopathic pulmonary fibrosis (IPF) share a common pathogenic mechanism, but the underlying mechanisms remain ambiguous. Our study aims at exploring the genetic-level pathogenic mechanism of these two diseases.MethodsWe carried out bioinformatics analysis on the GSE55235 and GSE213001 datasets. Machine learning was employed to identify candidate genes, which were further verified using the GSE92592 and GSE89408 datasets, as well as quantitative real-time PCR (qRT-PCR). The expression levels of TOP2A in RA and IPF in vitro models were confirmed using West

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… Anoikis and SPP1 in idiopathic pulmonary fibrosis: integrating bioinformatics, cell, and animal studies to explore prognostic biomarkers and PI3K/AKT signaling regulation. Expert Rev Clin Immunol . 2024;20:679–693. doi: 10.1080/1744666X.2024.2315218 31. Bugatti S, Manzo A, Benaglio F, et al. …

Minimally effective concentration of zoledronic acid to suppress osteoclasts in vitro.

Zoledronic acid is regarded as the most potent bisphosphonate and is widely used in patients with osteoporosis; however, its side effects, including acute-phase reactions, gastrointestinal complaints, renal dysfunction and bisphosphonate-associated osteonecrosis impair the safety and quality of life of patients. The present study was designed to determine the minimal effective concentration of zoledronic acid through testing the dose-dependent effects of zoledronic acid on osteoclast suppression. A primary culture of bone marrow mononuclear cells obtained from C57 mice (age, 6 weeks) was estab

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… Induction of cell death of human osteogenic sarcoma cells by zoledronic acid resembles anoikis. Bone. 2003;33:216–228. doi: 10.1016/S8756-3282(03)00223-0. 9. Majithia N, Atherton PJ, Lafky JM, Wagner-Johnston N, Olson J, Dakhil SR, Perez EA, Loprinzi CL, Hines SL. …

Selenium Compounds as Novel Potential Anticancer Agents.

The high number of new cancer incidences and the associated mortality continue to be alarming, leading to the search for new therapies that would be more effective and less burdensome for patients. As there is evidence that Se compounds can have chemopreventive activity, studies have begun to establish whether these compounds can also affect already existing cancers. This review aims to discuss the different classes of Se-containing compounds, both organic and inorganic, natural and synthetic, and the mechanisms and molecular targets of their anticancer activity. The chemical classes discussed

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… Non-apoptotic events may also occur, such as cell cycle arrest [ 3 , 7 , 12 ], necrosis [ 3 , 7 ], autophagy [ 7 , 12 ], ferroptosis [ 14 ], necroptosis [ 13 ], entosis [ 15 ], anoikis [ 8 , 16 ], NETosis [ 17 ], or mitotic catastrophe [ 7 ]. … Caspases as key executors of methyl selenium-induced apoptosis (Anoikis) of DU-145 prostate cancer cells. Cancer Res. 2001;61:3062–3070. 17. Zhang Y., Cartland S.P., Henriquez R., Patel S., Gammelgaard B., Flouda K., Hawkins C.L., Rayner B.S. …

Mechanisms of Resistance to Chemotherapy in Breast Cancer and Possible Targets in Drug Delivery Systems.

Breast cancer (BC) is one of the most important cancers worldwide, and usually, chemotherapy can be used in an integrative approach. Usually, chemotherapy treatment is performed in association with surgery, radiation or hormone therapy, providing an increased outcome to patients. However, tumors can develop resistance to different drugs, progressing for a more aggressive phenotype. In this scenario, the use of nanocarriers could help to defeat tumor cell resistance, providing a new therapeutic perspective for patients. Thus, this systematic review aims to bring the molecular mechanisms involve

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… MicroRNA-200a promotes anoikis resistance and metastasis by targeting YAP1 in human breast cancer Clin. Cancer Res. 2013 19 1389 1399 10.1158/1078-0432.CCR-12-1959 23340296 60. Zhang C.-M. Zhao Y. Deng H.-Y. …

The roles of Cryptochrome-1: the circadian clock as a control point in cancer therapy.

In this review, we carefully describe the composition and operation of cryptochrome-1 (CRY1). We introduce four related signaling pathways, namely cAMP/PKA/CREB signaling way, HIFα signaling way, NF-κB signaling way, STAT3 signaling way, FOXO signaling pathway and Hedgehog (HH) signaling pathway. We also emphasize the current understanding of the complex roles CRY1 plays in the progression of various solid tumors. We propose that its function represents a novel therapeutic target that could pave the way for new cancer treatments. Additionally, we summarize three emerging therapeutic strategies

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… An in vivo model of hepatocellular carcinoma, for instance, showed that autophagy facilitated the spread of metastases and anoikis resistance [ 243 ]. …

The role of autophagy in cancer: from molecular mechanism to therapeutic window.

Autophagy is a cellular degradation process that plays a crucial role in maintaining metabolic homeostasis under conditions of stress or nutrient deprivation. This process involves sequestering, breaking down, and recycling intracellular components such as proteins, organelles, and cytoplasmic materials. Autophagy also serves as a mechanism for eliminating pathogens and engulfing apoptotic cells. In the absence of stress, baseline autophagy activity is essential for degrading damaged cellular components and recycling nutrients to maintain cellular vitality. The relationship between autophagy a

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… Given the many challenges that metastatic tumor cells must overcome in order to successfully establish distant colonies (such as invasion, anoikis resistance, and colonization) and the essential role of autophagy as a response to cellular stress, various roles for autophagy in the metastatic cascade …