scholarly journals The extracellular matrix promotes breast cancer cell growth under amino acid starvation by promoting tyrosine catabolism

2021 ◽  
Author(s):  
Mona Nazemi ◽  
Bian Yanes ◽  
Montserrat Llanses Martinez ◽  
Heather Walker ◽  
Frederic Bard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Amino Acid ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Amino Acid Starvation ◽  
Metabolic Adaptation ◽  
Cancer Cell Growth

Breast cancer tumours are embedded in a collagen I rich extracellular matrix (ECM) network where nutrients are scarce due to limited blood flow and elevated tumour growth. Metabolic adaptation is required for breast cancer cells to endure these conditions. Here, we demonstrated that the presence of ECM supported the growth of invasive breast cancer cells, but not non-transformed mammary epithelial cells, under amino acid starvation, through a mechanism that required ECM uptake. Importantly, we showed that this behaviour was acquired during carcinoma progression. ECM internalisation, followed by lysosomal degradation, contributed to the upregulation of the intracellular levels of several amino acids, including tyrosine and phenylalanine. Finally, we showed that cells on ECM had elevated tyrosine catabolism, leading to elevated fumarate levels, potentially feeding into the tricarboxylic acid cycle. Interestingly, this pathway was required for ECM-dependent cell growth under amino acid starvation, as the knockdown of HPDL, the third enzyme of the pathway, opposed cell growth on ECM without affecting cell proliferation on plastic. Collectively, our results highlight that the ECM surrounding breast cancer tumours represents an alternative source of nutrients to support cancer cell growth, by regulating phenylalanine and tyrosine metabolism.

Gli activation by the estrogen receptor in breast cancer cells: Regulation of cancer cell growth by Gli3

2021 ◽  
Vol 522 ◽  
pp. 111136
Author(s):  
Shabnam Massah ◽  
Jane Foo ◽  
Na Li ◽  
Sarah Truong ◽  
Mannan Nouri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Growth

scholarly journals Globular Adiponectin Inhibits Breast Cancer Cell Growth through Modulation of Inflammasome Activation: Critical Role of Sestrin2 and AMPK Signaling

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 613 ◽  
Author(s):  
Duc-Vinh Pham ◽  
Pawan Kumar Raut ◽  
Mahesh Pandit ◽  
Jae-Hoon Chang ◽  
Nikita Katila ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Growth ◽  
Breast Cancer Cell Growth ◽  
Globular Adiponectin

Adiponectin, an adipokine predominantly derived from adipose tissue, exhibits potent antitumor properties in breast cancer cells. However, its mechanisms of action remain elusive. Inflammasomes—intracellular multimeric protein complexes—modulate cancer cell growth in a complicated manner, as well as playing a role in the innate immune system. Herein, we examined the potential role of inflammasomes in the antitumor activity of adiponectin and found that globular adiponectin (gAcrp) significantly suppressed inflammasomes activation in breast cancer cells both in vitro and in vivo conditions, as determined by decreased expression of inflammasomes components, including NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and the apoptosis-associated speck-like protein containing a CARD (ASC), and inhibition of interleukin-1β and caspase-1 activation. Treatment with pharmacological inhibitors of inflammasomes caused decrease in cell viability, apoptosis induction, and G0/G1 cell cycle arrest, suggesting that inflammasomes activation is implicated in the growth of breast cancer cells. In addition, treatment with gAcrp generated essentially similar results to those of inflammasomes inhibitors, further indicating that suppression of breast cancer cell growth by gAcrp is mediated via modulation of inflammasomes. Mechanistically, gAcrp suppressed inflammasomes activation through sestrin2 (SESN2) induction, liver kinase B1 (LKB-1)-dependent AMP-activated protein kinase (AMPK) phosphorylation, and alleviation of endoplasmic reticulum (ER) stress. Taken together, these results demonstrate that gAcrp inhibits growth of breast cancer cells by suppressing inflammasomes activation, at least in part, via SESN2 induction and AMPK activation-dependent mechanisms.

scholarly journals Characterising the Response of Human Breast Cancer Cells to Polyamine Modulation

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 743
Author(s):  
Oluwaseun Akinyele ◽  
Heather M. Wallace
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Growth Responses ◽  
Cancer Management ◽  
Mcf 7

Breast cancer is a complex heterogeneous disease with multiple underlying causes. The polyamines putrescine, spermidine, and spermine are polycationic molecules essential for cell proliferation. Their biosynthesis is upregulated in breast cancer and they contribute to disease progression. While elevated polyamines are linked to breast cancer cell proliferation, there is little evidence to suggest breast cancer cells of different hormone receptor status are equally dependent on polyamines. In this study, we characterized the responses of two breast cancer cells, ER+ (oestrogen receptor positive) MCF-7 and ER- MDA-MB-231 cell lines, to polyamine modulation and determined the requirement of each polyamine for cancer cell growth. The cells were exposed to DFMO (a polyamine pathway inhibitor) at various concentrations under different conditions, after which several growth parameters were determined. Exposure of both cell lines to DFMO induced differential growth responses, MCF-7 cells showed greater sensitivity to polyamine pathway inhibition at various DFMO concentrations than the MDA-MB-231 cells. Analysis of intracellular DFMO after withdrawal from growth medium showed residual DFMO in the cells with concomitant decreases in polyamine content, ODC protein level, and cell growth. Addition of exogenous polyamines reversed the cell growth inhibition, and this growth recovery appears to be partly dependent on the spermidine content of the cell. Similarly, DFMO exposure inhibits the global translation state of the cells, with spermidine addition reversing the inhibition of translation in the breast cancer cells. Taken together, these data suggest that breast cancer cells are differentially sensitive to the antitumour effects of polyamine depletion, thus, targeting polyamine metabolism might be therapeutically beneficial in breast cancer management based on their subtype.

scholarly journals TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth

2015 ◽  
Vol 112 (25) ◽  
pp. E3216-E3225 ◽  
Author(s):  
Svasti Haricharan ◽  
Powel Brown
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Breast Tumors ◽  
Wild Type ◽  
Cancer Cell Growth ◽  
Breast Cancer Cell Growth ◽  
Tlr4 Activation

Breast cancer is a leading cause of cancer-related death, and it is important to understand pathways that drive the disease to devise effective therapeutic strategies. Our results show that Toll-like receptor 4 (TLR4) drives breast cancer cell growth differentially based on the presence of TP53, a tumor suppressor. TP53 is mutationally inactivated in most types of cancer and is mutated in 30–50% of diagnosed breast tumors. We demonstrate that TLR4 activation inhibits growth of TP53 wild-type cells, but promotes growth of TP53 mutant breast cancer cells by regulating proliferation. This differential effect is mediated by changes in tumor cell cytokine secretion. Whereas TLR4 activation in TP53 mutant breast cancer cells increases secretion of progrowth cytokines, TLR4 activation in TP53 wild-type breast cancer cells increases type I IFN (IFN-γ) secretion, which is both necessary and sufficient for mediating TLR4-induced growth inhibition. This study identifies a novel dichotomous role for TLR4 as a growth regulator and a modulator of tumor microenvironment in breast tumors. These results have translational relevance, demonstrating that TP53 mutant breast tumor growth can be suppressed by pharmacologic TLR4 inhibition, whereas TLR4 inhibitors may in fact promote growth of TP53 wild-type tumors. Furthermore, using data generated by The Cancer Genome Atlas consortium, we demonstrate that the effect of TP53 mutational status on TLR4 activity may extend to ovarian, colon, and lung cancers, among others, suggesting that the viability of TLR4 as a therapeutic target depends on TP53 status in many different tumor types.

scholarly journals Starve Cancer Cells of Glutamine: Break the Spell or Make a Hungry Monster?

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 804 ◽  
Author(s):  
Jie Jiang ◽  
Sankalp Srivastava ◽  
Ji Zhang
Keyword(s):  
Amino Acid ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Therapeutic Strategy ◽  
Glutamine Metabolism ◽  
Cancer Cell Growth ◽  
Growth And Survival ◽  
Tumor Environment ◽  
Cell Growth And Survival

Distinct from normal differentiated tissues, cancer cells reprogram nutrient uptake and utilization to accommodate their elevated demands for biosynthesis and energy production. A hallmark of these types of reprogramming is the increased utilization of, and dependency on glutamine, a nonessential amino acid, for cancer cell growth and survival. It is well-accepted that glutamine is a versatile biosynthetic substrate in cancer cells beyond its role as a proteinogenic amino acid. In addition, accumulating evidence suggests that glutamine metabolism is regulated by many factors, including tumor origin, oncogene/tumor suppressor status, epigenetic alternations and tumor microenvironment. However, despite the emerging understanding of why cancer cells depend on glutamine for growth and survival, the contribution of glutamine metabolism to tumor progression under physiological conditions is still under investigation, partially because the level of glutamine in the tumor environment is often found low. Since targeting glutamine acquisition and utilization has been proposed to be a new therapeutic strategy in cancer, it is central to understand how tumor cells respond and adapt to glutamine starvation for optimized therapeutic intervention. In this review, we first summarize the diverse usage of glutamine to support cancer cell growth and survival, and then focus our discussion on the influence of other nutrients on cancer cell adaptation to glutamine starvation as well as its implication in cancer therapy.

scholarly journals Preparation of optimized lipid-coated calcium phosphate nanoparticles for enhanced in vitro gene delivery to breast cancer cells

2015 ◽  
Vol 3 (33) ◽  
pp. 6805-6812 ◽  
Author(s):  
Jie Tang ◽  
Li Li ◽  
Christopher B. Howard ◽  
Stephen M. Mahler ◽  
Leaf Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Calcium Phosphate ◽  
Cell Growth ◽  
Gene Delivery ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Cell Growth ◽  
Calcium Phosphate Nanoparticles ◽  
Transfection Agent

The optimized lipid coated calcium phosphate nanoparticles more efficiently deliver functional siRNA and inhibit the cancer cell growth, in comparison with the commercial transfection agent OligofactamineTM.

scholarly journals Crocetin shifts autophagic cell survival to death of breast cancer cells in chemotherapy

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769453 ◽  
Author(s):  
Ailian Zhang ◽  
Jincheng Li
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Cell Survival ◽  
Cancer Cells ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Growth ◽  
Breast Cancer Cell Growth ◽  
Treated Breast ◽  
Treated Breast Cancer

The chemotherapy with fluorouracil is not always effective, in which some breast cancer cells may survive the fluorouracil treatment through enhanced autophagy. Crocetin is the major constituent of saffron, a Chinese traditional herb, which has recently found to have multiple pharmacological effects, including anticancer. However, the effects of Crocetin on the outcome of fluorouracil therapy for breast cancer have not been studied. Here, we showed that fluorouracil treatment inhibited the growth of breast cancer cells, in either a Cell Counting Kit-8 assay or an MTT assay. Inhibition of autophagy further suppressed breast cancer cell growth, suggesting that the breast cancer cells increased autophagic cell survival during fluorouracil treatment. However, Crocetin significantly increased the suppressive effects of fluorouracil on breast cancer cell growth, without affecting either cell apoptosis or autophagy. Inhibition of autophagy at the presence of Crocetin partially abolished the suppressive effects on breast cancer cell growth, suggesting that Crocetin may increase autophagic cell death in fluorouracil-treated breast cancer cells. Furthermore, Crocetin decreased Beclin-1 levels but increased ATG1 levels in fluorouracil-treated breast cancer cells. Together, these data suggest that Crocetin may shift autophagic cell survival to autophagic cell death in fluorouracil-treated breast cancer cells, possibly through modulation of the expression of ATG1 and Beclin-1.

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