Therapeutic targeting of lipid synthesis metabolism for selective elimination of cancer stem cells

Kim, Woo Young

doi:10.1007/s12272-018-1098-z

Cited by 25 publications

(17 citation statements)

References 173 publications

(210 reference statements)

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“…extracellular rigidity (Dupont et al 2011;Dupont 2016;Pocaterra et al 2020). Although TAZ and YAP are paralogs with functional redundancy and tumor-promoting effects (Kim 2019), it is clear that TAZ and YAP play distinctively essential roles in normal tissue development and homeostasis (Yu et al 2015;Reggiani et al 2020). We clarify the The essential role of TAZ in normal tissue homeostasis genetic and protein structural features of TAZ and further highlight its biological functions in normal tissue differentiation from stem cells and in the regulation of tissue homeostasis.…”

Section: Introductionmentioning

confidence: 86%

The essential role of TAZ in normal tissue homeostasis

2021

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Transcriptional coactivator with PDZ-binding motif (TAZ) has been extensively characterized in organ development, tissue regeneration, and tumor progression. In particular, TAZ functions as a Hippo mediator that regulates organ size, tumor growth and migration. It is highly expressed in various types of human cancer, and has been reported to be associated with tumor metastasis and poor outcomes in cancer patients, suggesting that TAZ is an oncogenic regulator. Yes-associated protein (YAP) has 60% similarity in amino acid sequence to TAZ and plays redundant roles with TAZ in the regulation of cell proliferation and migration of cancer cells. Therefore, TAZ and YAP, which are encoded by paralogous genes, are referred to as TAZ/YAP and are suggested to be functionally equivalent. Despite its similarity to YAP, TAZ can be clearly distinguished from YAP based on its genetic, structural, and functional aspects. In addition, targeting superabundant TAZ can be a promising therapeutic strategy for cancer treatment; however, persistent TAZ inactivation may cause failure of tissue homeostatic control. This review focuses primarily on TAZ, not YAP, discusses its structural features and physiological functions in the regulation of tissue homeostasis, and provides new insights into the drug development targeting TAZ to control reproductive and musculoskeletal disorders.

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Section: Introductionmentioning

confidence: 86%

The essential role of TAZ in normal tissue homeostasis

2021

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“…SREBP2 and its target genes are markedly upregulated in prostate cancer, breast cancer, and HCC [61]. Cholesterol biosynthesis also plays an important role in the maintenance of cancer stem cells by activating sonic hedgehog and Notch pathway [62].…”

Section: Reprogrammed Cholesterol Metabolism In Cancer Cellsmentioning

confidence: 99%

Lipid Metabolism in Oncology: Why It Matters, How to Research, and How to Treat

Matsushita

Nakagawa

Koike

2021

Cancers

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Lipids in our body, which are mainly composed of fatty acids, triacylglycerides, sphingolipids, phospholipids, and cholesterol, play important roles at the cellular level. In addition to being energy sources and structural components of biological membranes, several types of lipids serve as signaling molecules or secondary messengers. Metabolic reprogramming has been recognized as a hallmark of cancer, but changes in lipid metabolism in cancer have received less attention compared to glucose or glutamine metabolism. However, recent innovations in mass spectrometry- and chromatography-based lipidomics technologies have increased our understanding of the role of lipids in cancer. Changes in lipid metabolism, so-called “lipid metabolic reprogramming”, can affect cellular functions including the cell cycle, proliferation, growth, and differentiation, leading to carcinogenesis. Moreover, interactions between cancer cells and adjacent immune cells through altered lipid metabolism are known to support tumor growth and progression. Characterization of cancer-specific lipid metabolism can be used to identify novel metabolic targets for cancer treatment, and indeed, several clinical trials are currently underway. Thus, we discuss the latest findings on the roles of lipid metabolism in cancer biology and introduce current advances in lipidomics technologies, focusing on their applications in cancer research.

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“…Lipid-associated pathways are essential for the maintenance of CSCs [66]. Lipid metabolism is inherently bound to the glucose and amino acid metabolic pathways in order to meet the increasing bio-energetic needs of CSCs.…”

Section: Correlation Of Ocsc Markers With Lipid Metabolismmentioning

confidence: 99%

Metabolic Plasticity in Ovarian Cancer Stem Cells

Ghoneum

Gonzalez

Abdulfattah

et al. 2020

Cancers

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Ovarian Cancer is the fifth most common cancer in females and remains the most lethal gynecological malignancy as most patients are diagnosed at late stages of the disease. Despite initial responses to therapy, recurrence of chemo-resistant disease is common. The presence of residual cancer stem cells (CSCs) with the unique ability to adapt to several metabolic and signaling pathways represents a major challenge in developing novel targeted therapies. The objective of this study is to investigate the transcripts of putative ovarian cancer stem cell (OCSC) markers in correlation with transcripts of receptors, transporters, and enzymes of the energy generating metabolic pathways involved in high grade serous ovarian cancer (HGSOC). We conducted correlative analysis in data downloaded from The Cancer Genome Atlas (TCGA), studies of experimental OCSCs and their parental lines from Gene Expression Omnibus (GEO), and Cancer Cell Line Encyclopedia (CCLE). We found positive correlations between the transcripts of OCSC markers, specifically CD44, and glycolytic markers. TCGA datasets revealed that NOTCH1, CD133, CD44, CD24, and ALDH1A1, positively and significantly correlated with tricarboxylic acid cycle (TCA) enzymes. OVCAR3-OCSCs (cancer stem cells derived from a well-established epithelial ovarian cancer cell line) exhibited enrichment of the electron transport chain (ETC) mainly in complexes I, III, IV, and V, further supporting reliance on the oxidative phosphorylation (OXPHOS) phenotype. OVCAR3-OCSCs also exhibited significant increase in CD36, ACACA, SCD, and CPT1A, with CD44, CD133, and ALDH1A1 exhibiting positive correlations with lipid metabolic enzymes. TCGA data show positive correlations between OCSC markers and glutamine metabolism enzymes, whereas in OCSC experimental models of GSE64999, GSE28799, and CCLE, the number of positive and negative correlations observed was significantly lower and was different between model systems. Appropriate integration and validation of data model systems with those in patients’ specimens is needed not only to bridge our knowledge gap of metabolic programing of OCSCs, but also in designing novel strategies to target the metabolic plasticity of dormant, resistant, and CSCs.

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Therapeutic targeting of lipid synthesis metabolism for selective elimination of cancer stem cells

Cited by 25 publications

References 173 publications

The essential role of TAZ in normal tissue homeostasis

The essential role of TAZ in normal tissue homeostasis

Lipid Metabolism in Oncology: Why It Matters, How to Research, and How to Treat

Metabolic Plasticity in Ovarian Cancer Stem Cells

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