Translational oncogenomics最新文献

Sirtuins are NAD(+)-dependent histone deacetylases (Class III HDACs). Recently, Sirtuins have been shown to play important roles, both direct and indirect, in transcriptional regulation. This transcriptional control, through incorporation of Sirtuins into transcription complexes and deacetylation of histones locally at gene promoters, or direct interaction with specific transcription factors, is central to the participation of Sirtuins in multiple diverse processes, including aging, apoptosis, hormone responses, stress tolerance, differentiation, metabolism and development. Here we review the contribution of the Sirtuin family, at multiple molecular levels, to transcriptional regulation.

In the last two decades there has been considerable progress in our understanding of the role of sphingolipids in controlling signal transduction processes, particularly in the mechanisms leading to regulation of cell growth and death. Ceramide is a well-characterized sphingolipid metabolite and second messenger that can be produced by cancer cells in response to a variety of stimuli, including therapeutic drugs, leading to cell cycle arrest and apoptosis. Although this is a promising aspect when thinking of treating cancer, it should be borne in mind that ceramide production may not always be a growth inhibitory or pro-apoptotic signal. In fact, ceramide can be readily converted to sphingosine 1-phosphate (S1P) by the concerted actions of ceramidases and sphingosine kinases, or to ceramide 1-phosphate (C1P) by the action of ceramide kinase. In general, S1P and C1P have opposing effects to ceramide, acting as pro-survival or mitogenic signals in most cell types. This review will address our current understanding of the many roles of ceramide, S1P and C1P in the regulation of cell growth and survival with special emphasis to the emerging role of these molecules and their metabolizing enzymes in controlling tumor progression and metastasis.

A great amount of literature has demonstrated a connection between obesity, visceral fat and the metabolic disorders such as hyperglycemia, hypertension, and hyperlipidemia. Lately, there has been an increased interest in understanding if cancer is related to obesity and visceral fat accumulation. The prevalence of both obesity and cancer are increasing and there has been keen interest in the relationship between visceral adiposity and the biology of cancers. White adipose tissue (WAT) provides a limitless capacity for triglyceride storage vital for survival. The concurrent rise in insulin, glucose, and lipids during meals stimulates triglyceride formation and storage in WAT. WAT is also recognized as an endocrine organ that secretes multiple cytokines such as leptin and adiponectin. In addition, leptin and adiponectin have been adipocytokines that attracted attention for cancer research. Thus, in this review, we will describe recent progress made in obesity, visceral adiposity, leptin and adiponectin in the involvement of various cancers.

Gene associated with retinoid-interferon-β-induced mortality (GRIM)-19, was originally identified as a critical regulatory protein necessary for Interferon-β-Retinoic acid-induced cell death. Overexpression of GRIM-19 activates cell death and its suppression or inactivation promotes cell growth. GRIM-19 targets multiple proteins/pathways for exerting growth control and cell death. However, GRIM-19 is also required for normal cellular processes. In addition, viruses 'hijack' GRIM-19 for their survival. Intracellular bacterial infections and bacterial products have been reported to induce the expression of GRIM-19. In this review, we will discuss the current status of GRIM-19 in growth control and innate immune response.

Prostate cancer is the second leading cause of cancer death among men in the United States of America. However, the molecular mechanisms underlying the disease remain largely unknown. Therefore, the identification of tumor specific molecules that serve as targets for the development of new cancer drugs is considered to be a major goal in cancer research. The mouse Engrailed-2 (En-2) gene, which is a homeobox-containing transcription factor was recently identified as a candidate oncogene in breast cancer. Here, we demonstrate that En-2 is over-expressed in human prostate cancer cells as compared to normal prostate epithelial cells. In addition, our data suggests that EN2 expression may be positively modulated by PAX2 transcription factor. Furthermore, down-regulation of EN2 expression by siRNA resulted in a decrease in PAX2 expression. We also provide evidence that down-regulation of EN2 expression causes a dramatic decrease in prostate cancer cell proliferation. Therefore, from our studies we conclude that En-2 is a candidate oncogene in prostate cancer and its PAX2-regulated expression contributes to prostate cancer cell growth.