125757
FCT-ANR/BEX-BCM/0175/2012
FCT - Fundação para a Ciência e a Tecnologia, I.P.
Portugal
3599-PPCDT
185,036.00 €
2013-04-01
2016-09-30
Tese de doutoramento do Programa Doutoral em Biologia Molecular e Ambiental (especialidade em Biologia Celular e Saúde); A decisive event in the cell‟s life-or-death decision is the mitochondrial outer membrane permeabilization (MOMP). The biochemical events responsible for MOMP, considered by many investigators the “point-of-no-return” in cell death, are not entirely defined. Two major and very distinct mechan...
Programa Doutoral em Biologia Molecular e Ambiental; Colorectal carcinoma (CRC) is the third most commonly diagnosed cancer worldwide and one of the most abundant causes of cancer related deaths. KRAS mutations ( KRASG13D, KRASG12D and KRASG12V) are frequent events in CRC, detected in about 30% to 50% of the clinical cases, and seem to play an important role in colon carcinogenesis. It is known that KRAS mutati...
The recent interest to modulate autophagy in cancer therapy has been hampered by the dual roles of this conserved catabolic process in cancer, highlighting the need for tailored approaches. Since RAS isoforms have been implicated in autophagy regulation and mutation of the KRAS oncogene is highly frequent in colorectal cancer (CRC), we questioned whether/how mutant KRAS alleles regulate autophagy in CRC and its...
Cathepsin D has garnered increased attention in recent years, mainly since it has been associated with several human pathologies. In particular, cathepsin D is often overexpressed and hypersecreted in cancer cells, implying it may constitute a therapeutic target. However, cathepsin D can have both anti- and pro-survival functions depending on its proteolytic activity, cellular context and stress stimulus. There...
Dissertação de mestrado em Bioquímica Aplicada; Apoptosis is a type of cell death, known as a highly regulated program of cellular suicide; however this process is often deregulated in tumor cells. A mechanism used by tumor cells to evade apoptosis is the alteration of the different members of the Bcl-2 family. These proteins control a key step in the intrinsic apoptotic pathway: permeabilization of the outer m...
Acetate, together with other short chain fatty acids has been implicated in colorectal cancer (CRC) prevention/therapy. Acetate was shown to induce apoptosis in CRC cells. The precise mechanism underlying acetate transport across CRC cells membrane, that may be implicated in its selectivity towards CRC cells, is not fully understood and was addressed here. We also assessed the effect of acetate in CRC glycolyti...
Breast cancer is the most common type of cancer affecting women. Despite the good prognosis when detected early, significant challenges remain in the treatment of metastatic breast cancer. The recruitment of the vacuolar H+-ATPase (V-H+-ATPase) to the plasma membrane, where it mediates the acidification of the tumor microenvironment (TME), is a recognized feature involved in the acquisition of a metastatic phen...
Cisplatin is a highly effective chemotherapeutic drug acting as a DNA-damaging agent that induces apoptosis of rapidly proliferating cells. Unfortunately, cellular resistance still occurs. Mutations in p53 in a large fraction of tumor cells contribute to defects in apoptotic pathways and drug resistance. To uncover new strategies to eliminate tumors through a p53-independent pathway, we established a simplified...
Proteins of the Bcl-2 protein family, including pro-apoptotic Bax and anti-apoptotic Bcl-xL, are critical for mitochondrial-mediated apoptosis regulation. Since yeast lacks obvious orthologs of Bcl-2 family members, heterologous expression of these proteins has been used to investigate their molecular and functional aspects. Active Bax is involved in the formation of mitochondrial outer membrane pores, through ...
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