Search results for "Cancer Stem Cells"
showing 10 items of 96 documents
HER2 Signaling and Breast Cancer Stem Cells: The Bridge behind HER2-Positive Breast Cancer Aggressiveness and Therapy Refractoriness
2021
Simple Summary Breast cancer (BC) is not a single disease, but a group of different tumors, and altered HER2 expression defines a particularly aggressive subtype. Although HER2 pharmacological inhibition has dramatically improved the prognosis of HER2-positive BC patients, there is still an urgent need for improved knowledge of HER2 biology and mechanisms underlying HER2-driven aggressiveness and drug susceptibility. Emerging data suggest that the clinical efficacy of molecularly targeted therapies is related to their ability to target breast cancer stem cells (BCSCs), a population that is not only self-sustaining and able to differentiate into distinct lineages, but also contributes to tum…
Dual Inhibition of Myc Transcription and PI3K Activity Effectively Targets Colorectal Cancer Stem Cells
2022
Despite advances in the curative approach, the survival rate of advanced colorectal cancer (CRC) patients is still poor, which is likely due to the emergence of cancer cell clones resistant to the available therapeutic options. We have already shown that CD44v6-positive CRC stem cells (CR-CSCs) are refractory toward standard anti-tumor therapeutic agents due to the activation of the PI3K pathway together with high HER2 expression levels. Tumor microenvironmental cytokines confer resistance to CR-CSCs against HER2/PI3K targeting by enhancing activation of the MAPK pathway. Here, we show that the CSC compartment, spared by BRAF inhibitor-based targeted therapy, is associated with increased ex…
Colorectal Cancer Stem Cells and Cell Death
2011
Nowadays it is reported that, similarly to other solid tumors, colorectal cancer is sustained by a rare subset of cancer stem-like cells (CSCs), which survive conventional anticancer treatments, hanks to efficient mechanisms allowing escape from apoptosis, triggering tumor recurrence. To improve patient outcomes, conventional anticancer therapies have to be replaced with specific approaches targeting CSCs. In this review we provide strong support that BMP4 is an innovative therapeutic approach to prevent colon cancer growth increasing differentiation markers expression and apoptosis. Recent data suggest that in colorectal CSCs, protection from apoptosis is achieved by interleukin-4 (IL-4) a…
Intratumoral Heterogeneity, Its Contribution to Therapy Resistance and Methodological Caveats to Assessment
2014
Cancer is one of the most urgent health issues of today. According to WHO, the number of cancer cases is expected to increase by 75% in the next two decades (1). Despite some remarkable achievements in the fields of cancer prevention and early detection, the goal of developing effective anti-cancer therapies still remains unmet. Tumor recurrence due to treatment resistance is the most common cause of death from cancer. Delineating cellular and molecular mechanisms underlying tumor recurrence is of prime importance for the ability to improve the efficacy of existing therapies and develop new strategies to cancer treatment.
Dissecting the Mechanism of Action of Spiperone—A Candidate for Drug Repurposing for Colorectal Cancer
2022
Approximately 50% of colorectal cancer (CRC) patients still die from recurrence and metastatic disease, highlighting the need for novel therapeutic strategies. Drug repurposing is attracting increasing attention because, compared to traditional de novo drug discovery processes, it may reduce drug development periods and costs. Epidemiological and preclinical evidence support the antitumor activity of antipsychotic drugs. Herein, we dissect the mechanism of action of the typical antipsychotic spiperone in CRC. Spiperone can reduce the clonogenic potential of stem-like CRC cells (CRC-SCs) and induce cell cycle arrest and apoptosis, in both differentiated and CRC-SCs, at clinically relevant co…
Instruction of haematopoietic lineage choices, evolution of transcriptional landscapes and cancer stem cell hierarchies derived from an AML1-ETO mous…
2013
The t(8;21) chromosomal translocation activates aberrant expression of the AML1-ETO (AE) fusion protein and is commonly associated with core binding factor acute myeloid leukaemia (CBF AML). Combining a conditional mouse model that closely resembles the slow evolution and the mosaic AE expression pattern of human t(8;21) CBF AML with global transcriptome sequencing, we find that disease progression was characterized by two principal pathogenic mechanisms. Initially, AE expression modified the lineage potential of haematopoietic stem cells (HSCs), resulting in the selective expansion of the myeloid compartment at the expense of normal erythro- and lymphopoiesis. This lineage skewing was foll…
MicroRNA-29b-1 impairs in vitro cell proliferation, self‑renewal and chemoresistance of human osteosarcoma 3AB-OS cancer stem cells
2014
Osteosarcoma (OS) is the most common type of bone cancer, with a peak incidence in the early childhood. Emerging evidence suggests that treatments targeting cancer stem cells (CSCs) within a tumor can halt cancer and improve patient survival. MicroRNAs (miRNAs) have been implicated in the maintenance of the CSC phenotype, thus, identification of CSC-related miRNAs would provide information for a better understanding of CSCs. Downregulation of miRNA-29 family members (miR-29a/b/c; miR‑29s) was observed in human OS, however, little is known about the functions of miR-29s in human OS CSCs. Previously, during the characterization of 3AB-OS cells, a CSC line selected from human OS MG63 cells, we…
GSK-3 as potential target for therapeutic intervention in cancer
2014
// James A. McCubrey 1 , Linda S. Steelman 1 , Fred E. Bertrand 2 , Nicole M. Davis 1 , Melissa Sokolosky 1 , Steve L. Abrams 1 , Giuseppe Montalto 3 , Antonino B. D’Assoro 4 , Massimo Libra 5 , Ferdinando Nicoletti 5 , Roberta Maestro 6 , Jorg Basecke 7,8 , Dariusz Rakus 9 , Agnieszka Gizak 9 Zoya Demidenko 10 , Lucio Cocco 11 , Alberto M. Martelli 11 and Melchiorre Cervello 12 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University Greenville, NC, USA 2 Department of Oncology, Brody School of Medicine at East Carolina University Greenville, NC, USA 3 Biomedical Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy …
Genetic and Molecular Characterization of The Human Osteosarcoma 3AB-OS Cancer Stem Cell Line: A Possible Model For Studying Osteosarcoma Origin and …
2013
Finding new treatments targeting cancer stem cells (CSCs) within a tumor seems to be critical to halt cancer and improve patient survival. Osteosarcoma is an aggressive tumor affecting adolescents, for which there is no second-line chemotherapy. Uncovering new molecular mechanisms underlying the development of osteosarcoma and origin of CSCs is crucial to identify new possible therapeutic strategies. Here, we aimed to characterize genetically and molecularly the human osteosarcoma 3AB-OS CSC line, previously selected from MG63 cells and which proved to have both in vitro and in vivo features of CSCs. Classic cytogenetic studies demonstrated that 3AB-OS cells have hypertriploid karyotype wit…
TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells
2015
Metastatic growth in breast cancer (BC) has been proposed as an exclusive property of cancer stem cells (CSCs). However, formal proof of their identity as cells of origin of recurrences at distant sites and the molecular events that may contribute to tumor cell dissemination and metastasis development are yet to be elucidated. In this study, we analyzed a set of patient-derived breast cancer stem cell (BCSC) lines. We found that in vitro BCSCs exhibit a higher chemoresistance and migratory potential when compared with differentiated, nontumorigenic, breast cancer cells (dBCCs). By developing an in vivo metastatic model simulating the disease of patients with early BC, we observed that BCSCs…