The Flick of a Switch: Conferring Survival Advantage to Breast Cancer Stem Cells Through Metabolic Plasticity

Within heterogeneous tumors, cancer stem cell (CSC) populations exhibit the greatest tumor initiation potential, promote metastasis, and contribute to therapy resistance. For breast cancer specifically, CSCs are identified by CD44highCD24low cell surface marker expression and increased aldehyde dehydrogenase activity. In general, bulk breast tumor cells possess altered energetics characterized by aerobic glycolysis. In contrast, breast CSCs appear to have adaptive metabolic plasticity that allows these tumor-initiating cells to switch between glycolysis and oxidative phosphorylation, depending on factors present in the tumor microenvironment (e.g. hypoxia, reactive oxygen species, availability of glucose). In this article, we review the regulatory molecules that may facilitate the metabolic plasticity of breast CSCs. These regulatory factors include epigenetic chromatin modifiers, non-coding RNAs, transcriptional repressors, transcription factors, energy and stress sensors, and metabolic enzymes. Furthermore, breast cancer cells acquire CSC-like characteristics and altered energetics by undergoing epithelial-mesenchymal transition (EMT). This energy costly process is paired with reprogrammed glucose metabolism by epigenetic modifiers that regulate expression of both EMT and other metabolism-regulating genes. The survival advantage imparted to breast CSCs by metabolic plasticity suggests that targeting the factors that mediate the energetic switch should hinder tumorigenesis a...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research

Related Links:

i H. G. Wright Miguel Beato The growth of cancer cells as oncospheres in three-dimensional (3D) culture provides a robust cell model for understanding cancer progression, as well as for early drug discovery and validation. We have previously described a novel pathway in breast cancer cells, whereby ADP (Adenosine diphosphate)-ribose derived from hydrolysis of poly (ADP-Ribose) and pyrophosphate (PPi) are converted to ATP, catalysed by the enzyme NUDT5 (nucleotide diphosphate hydrolase type 5). Overexpression of the NUDT5 gene in breast and other cancer types is associated with poor prognosis, increased risk of recurr...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Abstract Triple negative breast cancer (TNBC) is a highly heterogeneous disease, which influences the therapeutic response and makes difficult the discovery of effective targets. This heterogeneity is attributed to the presence of breast cancer stem cells (BCSCs), which determines resistance to chemotherapy and subsequently disease recurrence and metastasis. In this context, this work aimed to evaluate the morphological and phenotypic cellular heterogeneity of two TNBC cell lines cultured in monolayer and tumorsphere (TS) models by fluorescence and electron microscopy and flow cytometry. The BT-549 and Hs 578T ana...
Source: European Biophysics Journal : EBJ - Category: Physics Authors: Tags: Eur Biophys J Source Type: research
In this study, we tested the hypothesis that EMP2 may regulate the formation or self-renewal of breast cancer stem cells (BCSC) in the tumor microenvironment.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Targeting CSC in a Most Aggressive Subtype of Breast Cancer TNBC. Adv Exp Med Biol. 2019;1152:311-334 Authors: Bao B, Prasad AS Abstract Triple negative breast cancer (TNBC) is a more aggressive subtype of breast cancer and is characteristic of the absence of the expressions of estrogen receptor, progesterone receptor, and human epithelial growth factor receptor 2 in breast tumor tissues. This subtype of breast cancer has the poorest prognosis, compared to other subtypes of breast cancer. TNBC is heterogeneous by showing several different histo-pathological and molecular subtypes with different pr...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Raouf The epithelial cells in an adult woman’s breast tissue are continuously replaced throughout their reproductive life during pregnancy and estrus cycles. Such extensive epithelial cell turnover is governed by the primitive mammary stem cells (MaSCs) that proliferate and differentiate into bipotential and lineage-restricted progenitors that ultimately generate the mature breast epithelial cells. These cellular processes are orchestrated by tightly-regulated paracrine signals and crosstalk between breast epithelial cells and their tissue microenvironment. However, current evidence suggests that alterations ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Rao The full epigenetic repertoire governing breast cancer metastasis is not completely understood. Here, we discuss the histone methyltransferase SET Domain Bifurcated Histone Lysine Methyltransferase 1 (SETDB1) and its role in breast cancer metastasis. SETDB1 serves as an exemplar of the difficulties faced when developing therapies that not only specifically target cancer cells but also the more elusive and aggressive stem cells that contribute to metastasis via epithelial-to-mesenchymal transition and confer resistance to therapies.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Cancers, Vol. 11, Pages 1128: CSCs in Breast Cancer—One Size Does Not Fit All: Therapeutic Advances in Targeting Heterogeneous Epithelial and Mesenchymal CSCs Cancers doi: 10.3390/cancers11081128 Authors: Andrew Sulaiman Sarah McGarry Xianghui Han Sheng Liu Lisheng Wang Unlike other breast cancer subtypes, triple-negative breast cancer (TNBC) has no specific targets and is characterized as one of the most aggressive subtypes of breast cancer that disproportionately accounts for the majority of breast cancer-related deaths. Current conventional chemotherapeutics target the bulk tumor population, but no...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
maswamy The hedgehog (Hh) pathway plays a key role in embryonic development and stem cell programs. Deregulation of the Hh pathway is a key driver of basal cell carcinoma, and therapeutic targeting led to approval of Hh inhibitor, vismodegib, in the management of this cancer. The Hh pathway is implicated in other malignancies including hormone receptor (HR+) positive and triple negative breast cancer (TNBC). Hh signaling, which is activated in human mammary stem cells, results in activation of glioma-associated oncogene (GLI) transcription factors. High GLI1 expression correlates with worse outcomes in breast cancer. N...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
AbstractPurpose of ReviewThere are over 700,000 cases of end-stage renal disease in the USA, resulting in more deaths per year than prostate or breast cancer. Many researchers have proposed the generation of in vitro kidney models or implantable therapeutic replacements using biomedical engineering strategies. Because the functional unit of the kidney —the nephron—is based on tubule structures, the formation of biosynthetic tubules is at the foundation of creating models or devices to recapitulate the kidney.Recent FindingsRecent approaches to engineering kidney tubules involve both bioengineering (perfusable m...
Source: Current Transplantation Reports - Category: Transplant Surgery Source Type: research
More News: Breast Cancer | Cancer | Cancer & Oncology | Epithelial Cancer | Genetics | Stem Cell Therapy | Stem Cells