RESUMO
An accelerated de novo lipogenesis (DNL) flux is a common characteristic of cancer cells required to sustain a high proliferation rate. The DNL enzyme fatty acid synthase (FASN) is overexpressed in many cancers and is pivotal for the increased production of fatty acids. There is increasing evidences of the involvement of FASN in several hallmarks of cancer linked to its ability to promote cell proliferation via membranes biosynthesis. In this review we discuss about the implication of FASN in the resistance to cell death and in the deregulation of cellular energetics by increasing nucleic acids, protein and lipid synthesis. FASN also promotes cell proliferation, cell invasion, metastasis and angiogenesis by enabling the building of lipid rafts and consequently to the localization of oncogenic receptors such as HER2 and c-Met in membrane microdomains. Finally, FASN is involved in immune escape by repressing the activation of pro-inflammatory cells and promoting the recruitment of M2 macrophages and T regulatory cells in the tumor microenvironment. Here, we provide an overview of the involvement of the pro-oncogenic enzyme in the hallmarks of cancer making FASN a promising target in anti-cancer therapy to circumvent resistance to chemotherapies.
RESUMO
Pancreatic cancer (PC) is a major cause of cancer-associated mortality in Western countries (and estimated to be the second cause of cancer deaths by 2030). The main form of PC is pancreatic adenocarcinoma, which is the fourth most common cause of cancer-related death, and this situation has remained virtually unchanged for several decades. Pancreatic ductal adenocarcinoma (PDAC) is inherently linked to the unique physiology and microenvironment of the exocrine pancreas, such as pH, mechanical stress, and hypoxia. Of them, calcium (Ca2+) signals, being pivotal molecular devices in sensing and integrating signals from the microenvironment, are emerging to be particularly relevant in cancer. Mutations or aberrant expression of key proteins that control Ca2+ levels can cause deregulation of Ca2+-dependent effectors that control signaling pathways determining the cells' behavior in a way that promotes pathophysiological cancer hallmarks, such as enhanced proliferation, survival and invasion. So far, it is essentially unknown how the cancer-associated Ca2+ signaling is regulated within the characteristic landscape of PDAC. This work provides a complete overview of the Ca2+ signaling and its main players in PDAC. Special consideration is given to the Ca2+ signaling as a potential target in PDAC treatment and its role in drug resistance.
