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Articles 1 - 6 of 6

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Metabolic Reprogramming Of Pancreatic Ductal Adenocarcinoma Cells In Response To Chronic Low Ph Stress, Jaime Abrego Dec 2017

Metabolic Reprogramming Of Pancreatic Ductal Adenocarcinoma Cells In Response To Chronic Low Ph Stress, Jaime Abrego

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of all cancers with a 5-year survival rate of only 8.2%. This is because PDAC is diagnosed in its advanced stages and is characterized by radio and chemotherapy resistance. Aggressiveness of PDAC tumors is attributed to its high metabolic phenotype, which is characterized by increased glycolysis rate and lactate secretion, while oxidative metabolism is reduced. These metabolic features are required to fulfill the biosynthetic demands of proliferating PDAC cells. However, this increase in metabolic activity results in acidification of the extracellular space because the dense fibrotic stroma of PDAC tumors ...


Critical Role For Arginase 2 In Obesity-Associated Pancreatic Cancer, Tamara Zaytouni, Pei-Yun Tsai, Daniel S. Hitchcock, Cory D. Dubois, Elizaveta Freinkman, Lin Lin, Vicente Morales-Oyarvide, Patrick J. Lenehan, Brian M. Wolpin, Mari Mino-Kenudson, Eduardo M. Torres, Nicholas Stylopoulos, Clary B. Clish, Nada Y. Kalaany Aug 2017

Critical Role For Arginase 2 In Obesity-Associated Pancreatic Cancer, Tamara Zaytouni, Pei-Yun Tsai, Daniel S. Hitchcock, Cory D. Dubois, Elizaveta Freinkman, Lin Lin, Vicente Morales-Oyarvide, Patrick J. Lenehan, Brian M. Wolpin, Mari Mino-Kenudson, Eduardo M. Torres, Nicholas Stylopoulos, Clary B. Clish, Nada Y. Kalaany

UMass Metabolic Network Publications

Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Despite recent identification of metabolic alterations in this lethal malignancy, the metabolic dependencies of obesity-associated PDA remain unknown. Here we show that obesity-driven PDA exhibits accelerated growth and a striking transcriptional enrichment for pathways regulating nitrogen metabolism. We find that the mitochondrial form of arginase (ARG2), which hydrolyzes arginine into ornithine and urea, is induced upon obesity, and silencing or loss of ARG2 markedly suppresses PDA. In vivo infusion of (15)N-glutamine in obese mouse models of PDA demonstrates enhanced nitrogen flux into the urea cycle and infusion of ...


The Brg1 Atpase Of Human Swi/Snf Chromatin Remodeling Enzymes As A Driver Of Cancer, Qiong Wu, Jane B. Lian, Janet L. Stein, Gary S. Stein, Jeffrey A. Nickerson, Anthony N. Imbalzano Jun 2017

The Brg1 Atpase Of Human Swi/Snf Chromatin Remodeling Enzymes As A Driver Of Cancer, Qiong Wu, Jane B. Lian, Janet L. Stein, Gary S. Stein, Jeffrey A. Nickerson, Anthony N. Imbalzano

Pediatric Publications and Presentations

Mammalian SWI/SNF enzymes are ATP-dependent remodelers of chromatin structure. These multisubunit enzymes are heterogeneous in composition; there are two catalytic ATPase subunits, BRM and BRG1, that are mutually exclusive, and additional subunits are incorporated in a combinatorial manner. Recent findings indicate that approximately 20% of human cancers contain mutations in SWI/SNF enzyme subunits, leading to the conclusion that the enzyme subunits are critical tumor suppressors. However, overexpression of specific subunits without apparent mutation is emerging as an alternative mechanism by which cellular transformation may occur. Here we highlight recent evidence linking elevated expression of the BRG1 ATPase to ...


Mammalian Swi/Snf Enzymes And The Epigenetics Of Tumor Cell Metabolic Reprogramming, Jeffrey A. Nickerson, Qiong Wu, Anthony N. Imbalzano Apr 2017

Mammalian Swi/Snf Enzymes And The Epigenetics Of Tumor Cell Metabolic Reprogramming, Jeffrey A. Nickerson, Qiong Wu, Anthony N. Imbalzano

UMass Metabolic Network Publications

Tumor cells reprogram their metabolism to survive and grow in a challenging microenvironment. Some of this reprogramming is performed by epigenetic mechanisms. Epigenetics is in turn affected by metabolism; chromatin modifying enzymes are dependent on substrates that are also key metabolic intermediates. We have shown that the chromatin remodeling enzyme Brahma-related gene 1 (BRG1), an epigenetic regulator, is necessary for rapid breast cancer cell proliferation. The mechanism for this requirement is the BRG1-dependent transcription of key lipogenic enzymes and regulators. Reduction in lipid synthesis lowers proliferation rates, which can be restored by palmitate supplementation. This work has established BRG1 as ...


Investigating The Roles Of P63 And P73 Isoforms To Therapeutically Treat P53-Altered Cancers, Avinashnarayan Venkatanarayan May 2015

Investigating The Roles Of P63 And P73 Isoforms To Therapeutically Treat P53-Altered Cancers, Avinashnarayan Venkatanarayan

UT GSBS Dissertations and Theses (Open Access)

Investigating the roles of p63 & p73 isoforms to therapeutically treat

p53-altered cancers

Avinashnarayan Venkatanarayan, M.S.

Supervisory Professor: Elsa R. Flores, Ph.D.

The TP53 tumor suppressor is mutated in approximately 50% of human cancers rendering cancer therapies ineffective. p53 reactivation suppresses tumor formation in mice. However, this strategy has proven difficult to implement therapeutically. An alternate approach to overcome p53 loss is to manipulate the p53-family members, p63 and p73, which interact and share structural similarities to p53. p63 and p73, unlike p53 are less frequently mutated and have two major isoforms with distinct functions which makes them ...


A Study On The Function Of 14-3-3sigma In Regulating Cancer Energy Metabolism, Liem M. Phan, Liem M. Phan Dec 2012

A Study On The Function Of 14-3-3sigma In Regulating Cancer Energy Metabolism, Liem M. Phan, Liem M. Phan

UT GSBS Dissertations and Theses (Open Access)

Metabolic reprogramming has been shown to be a major cancer hallmark providing tumor cells with significant advantages for survival, proliferation, growth, metastasis and resistance against anti-cancer therapies. Glycolysis, glutaminolysis and mitochondrial biogenesis are among the most essential cancer metabolic alterations because these pathways provide cancer cells with not only energy but also crucial metabolites to support large-scale biosynthesis, rapid proliferation and tumorigenesis. In this study, we find that 14-3-3σ suppresses all these three metabolic processes by promoting the degradation of their main driver, c-Myc. In fact, 14-3-3s significantly enhances c-Myc poly-ubiquitination and subsequent degradation, reduces c-Myc transcriptional activity, and down-regulates ...