Expression and associated epigenetic mechanisms of the Ca2+-signaling genes in breast cancer subtypes and epithelial-to-mesenchymal transition

Efficient catabolic metabolism of adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) is essentially required for cancer cell survival, especially in metastatic cancer progression. Epithelial–mesenchymal transition (EMT) plays an important role in metabolic rewiring of cancer cells as well as in phenotypic conversion and therapeutic resistance. Snail (SNAI1), a well-known inducer of cancer EMT, is critical in providing ATP and NADPH via suppression of several gatekeeper genes involving catabolic metabolism, such as phosphofructokinase 1 (PFK1), fructose-1,6-bisphosphatase 1 (FBP1), and acetyl-CoA carboxylase 2 (ACC2). Paradoxically, PFK1 and FBP1 are counter-opposing and rate-limiting reaction enzymes of glycolysis and gluconeogenesis, respectively. In this study, we report a distinct metabolic circuit of catabolic metabolism in breast cancer subtypes. Interestingly, PFKP and FBP1 are inversely correlated in clinical samples, indicating different metabolic subsets of breast cancer. The luminal types of breast cancer consist of the pentose phosphate pathway (PPP) subset by suppression of PFKP while the basal-like subtype (also known as triple negative breast cancer, TNBC) mainly utilizes glycolysis and mitochondrial fatty acid oxidation (FAO) by loss of FBP1 and ACC2. Notably, PPP remains active via upregulation of TIGAR in the FBP1-loss basal-like subset, indicating the importance of PPP in catabolic cancer metabolism. These results indicate different catabolic metabolic circuits and thus therapeutic strategies in breast cancer subsets.

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The Dicyano Compound Induces Autophagic or Apoptotic Cell Death Via Twıst/C-Myc Axis Depending on Metastatic Characteristics of Breast Cancer Cells

10.21203/rs.3.rs-590805/v1 ◽

2021 ◽

Author(s):

Ozge ALVUR ◽

Hakan KUCUKSAYAN ◽

Yasemin BAYGU ◽

Nilgun KABAY ◽

Yasar GOK ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cell Lines ◽

Epithelial To Mesenchymal Transition ◽

Apoptotic Cell ◽

Treatment Strategies ◽

Breast Cancer Cell Lines ◽

Mesenchymal Transition ◽

Cancer Subtypes ◽

Mcf 7

Abstract Breast cancer is a heterogeneous disease which has distinct subtypes and therefore development of novel targeting treatments to fight aganist breast cancer is needed. Although autophagy and apoptosis considered as the major programmed cell death mechanisms are among the current target mechanisms, there are some difficulties in clinical treatment such as the development of drug resistance and cancer recurrence. Therefore it is important that illumination of distinctive mechanisms between cancer types for development novel treatment strategies. In this study, we examined the anti-proliferative effects of the triazole linked galactose substituted dicyano compound (hereafter referred to as the dicyano compound (the DC)) on two different breast cancer cell lines, MDA-MB-231 and MCF-7. We determined that response of each cell lines to the DC was different, since autophagy was induced in MDA-MB-231 and apoptosis was induced in MCF-7. For this reason, we hypothesized that these different responses may be due to the different characteristics of the cells and evaluated effects of aggresiveness degrees of both cell lines on response to the DC. As a result of our analysis, we determined that c-Myc regulation in both cell lines was different upon the DC treatment depending on expression of Twist, an epithelial-to-mesenchymal transition (EMT) mediator. Therefore, we suggest that Twist/c-Myc axis may have a role in different response to the DC-induced cell death pathways in breast cancer subtypes.

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Store-Operated Ca2+ Entry in Breast Cancer Cells: Remodeling and Functional Role

International Journal of Molecular Sciences ◽

10.3390/ijms19124053 ◽

2018 ◽

Vol 19 (12) ◽

pp. 4053 ◽

Cited By ~ 15

Author(s):

Isaac Jardin ◽

Jose Lopez ◽

Gines Salido ◽

Juan Rosado

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Functional Role ◽

Breast Cancer Cells ◽

Epithelial To Mesenchymal Transition ◽

Molecular Subtype ◽

Luminal A ◽

Extracellular Medium ◽

Mesenchymal Transition ◽

Cancer Subtypes

Breast cancer is the most common type of cancer in women. It is a heterogeneous disease that ranges from the less undifferentiated luminal A to the more aggressive basal or triple negative breast cancer molecular subtype. Ca2+ influx from the extracellular medium, but more specifically store-operated Ca2+ entry (SOCE), has been reported to play an important role in tumorigenesis and the maintenance of a variety of cancer hallmarks, including cell migration, proliferation, invasion or epithelial to mesenchymal transition. Breast cancer cells remodel the expression and functional role of the molecular components of SOCE. This review focuses on the functional role and remodeling of SOCE in breast cancer cells. The current studies suggest the need to deepen our understanding of SOCE in the biology of the different breast cancer subtypes in order to develop new and specific therapeutic strategies.

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