Pancreatic cancer biology and genetics from an evolutionary perspective

Makohon-Moore, Alvin; Iacobuzio‐Donahue, Christine A.

doi:10.1038/nrc.2016.66

Cited by 332 publications

(268 citation statements)

References 138 publications

(213 reference statements)

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“…The diversity is achieved as transformed cells accumulate mutations. This leads to changes in signal transduction, the epigenome, and gene expression, which endow a spectrum of differentiation, metabolic, and proliferative states across the cancer cell populations in the tumor [2, 3]. These features encompass the intrinsic metabolic properties of the cancer cells [4–6].…”

Section: Features Of the Tumor Microenvironment That Affect Metabolismmentioning

confidence: 99%

Metabolic Interactions in the Tumor Microenvironment

Lyssiotis

Kimmelman

2017

Trends in Cell Biology

630

500

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Tumors are dynamic pseudo-organs that contain numerous cell types interacting to create unique physiology. Within this network, the malignant cells encounter many challenges and rewire their metabolic properties accordingly. Such changes can be experienced and executed autonomously or through interaction with other cells in the tumor. The focus of this review is on the remodeling of the tumor microenvironment that leads to pathophysiologic interactions that are influenced and shaped by metabolism. They include symbiotic nutrient sharing, nutrient competition, and the role of metabolites as signaling molecules. Examples of such processes abound in normal organismal physiology, and such heterocelluar metabolic interactions are repurposed to support tumor metabolism and growth. The importance and ubiquity of these processes is just beginning to be realized, and insights into their role in tumor development and progression are being used to design new drug targets and cancer therapies.

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Section: Features Of the Tumor Microenvironment That Affect Metabolismmentioning

confidence: 99%

Metabolic Interactions in the Tumor Microenvironment

Lyssiotis

Kimmelman

2017

Trends in Cell Biology

630

500

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“…Clonal expansion and progression to PanIN3 and PDAC requires additional signalling and mutational events to overcome oncogene-induced senescence, such as loss of cyclin-dependent kinase inhibitor 2A (CDKN2A, also known as p16 INK4A ). Eventually, additional inactivating mutations of tumour suppressor genes, such as Tp53 , Brca2 and Smad4 , occur during PanIN2 or PanIN3 progression, but at reduced rates (a detailed review on pancreatic cancer biology and genetics and photomicrographs of different lesions can be found elsewhere 100 ). However, comparative studies of human tissues and transgenic mice ( Pdx1- Cre; Kras LSL-G12D model) suggest that dysplastic lesions other than PanIN can also arise from ADM.…”

Section: Adm As a Precursor Lesionmentioning

confidence: 99%

Acinar cell plasticity and development of pancreatic ductal adenocarcinoma

Störz

2017

Nat Rev Gastroenterol Hepatol

256

273

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Acinar cells in the adult pancreas show high plasticity and can undergo transdifferentiation to a progenitor-like cell type with ductal characteristics. This process, termed acinar-to-ductal metaplasia (ADM), is an important feature facilitating pancreas regeneration after injury. Data from animal models show that cells that undergo ADM in response to oncogenic signalling are precursors for pancreatic intraepithelial neoplasia lesions, which can further progress to pancreatic ductal adenocarcinoma (PDAC). As human pancreatic adenocarcinoma is often diagnosed at a stage of metastatic disease, understanding the processes that lead to its initiation is important for the discovery of markers for early detection, as well as options that enable an early intervention. Here, the critical determinants of acinar cell plasticity are discussed, in addition to the intracellular and extracellular signalling events that drive acinar cell metaplasia and their contribution to development of PDAC.

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“…The major histological subtype is pancreatic ductal adenocarcinoma (PDAC), which accounts for over 90% of pancreatic cancer. PDACs originate from pancreatic ductal epithelium and evolve from premalignant lesions to fully invasive cancer with successive accumulation of gene mutations [149,150]. Since SMAD4 is identical to a putative tumor suppressor gene "deleted in pancreatic cancer locus 4, DPC4" [151], there have been extensive efforts to clarify the impact of this pathway on the development of PDACs.…”

Section: Pancreatic Cancer and Tgf-β Signalingmentioning

confidence: 99%

Intracellular and extracellular TGF-β signaling in cancer: some recent topics

et al. 2018

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Transforming growth factor (TGF)-β regulates a wide variety of cellular responses, including cell growth arrest, apoptosis, cell differentiation, motility, invasion, extracellular matrix production, tissue fibrosis, angiogenesis, and immune function. Although tumor-suppressive roles of TGF-β have been extensively studied and well-characterized in many cancers, especially at early stages, accumulating evidence has revealed the critical roles of TGF-β as a pro-tumorigenic factor in various types of cancer. This review will focus on recent findings regarding epithelial-mesenchymal transition (EMT) induced by TGF-β, in relation to crosstalk with some other signaling pathways, and the roles of TGF-β in lung and pancreatic cancers, in which TGF-β has been shown to be involved in cancer progression. Recent findings also strongly suggested that targeting TGF-β signaling using specific inhibitors may be useful for the treatment of some cancers. TGF-β plays a pivotal role in the differentiation and function of regulatory T cells (Tregs). TGF-β is produced as latent high molecular weight complexes, and the latent TGF-β complex expressed on the surface of Tregs contains glycoprotein A repetitions predominant (GARP, also known as leucine-rich repeat containing 32 or LRRC32). Inhibition of the TGF-β activities through regulation of the latent TGF-β complex activation will be discussed.

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Pancreatic cancer biology and genetics from an evolutionary perspective

Cited by 332 publications

References 138 publications

Metabolic Interactions in the Tumor Microenvironment

Metabolic Interactions in the Tumor Microenvironment

Acinar cell plasticity and development of pancreatic ductal adenocarcinoma

Intracellular and extracellular TGF-β signaling in cancer: some recent topics

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