METABOLISMCONNECT · Can metabolic states induced by diabetes and obesity promote cancer?
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2013-10-01 → 2017-09-30
- Финансиране от ЕС
- 100 000 €
- Участници
- 1
- Схема
- MC-CIG
Линиите свързват координатора с партньорите.
Накратко на български
Метаболитните промени в черния дроб, предизвикани от затлъстяването и диабета, се анализират чрез мишарски модели. Разбирането на тези процеси помага за подобряване на превенцията и лечението на рака при пациенти с наднормално тегло.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Can metabolic states induced by diabetes and obesity promote cancer?
Cancer is the second leading cause of death worldwide. An emerging risk factor for cancer is obesity and diabetes. Already today 30% of the liver cancer incidences are associated with obesity and subsequent diabetes. Moreover, obese patients have a 2-5 times increased risk of liver cancer mortality. Unfortunately, current links between obesity and cancer such as increased inflammation can only partially explain this strong correlation and have not led so far to an improved treatment schema for obese liver cancer patients or preventative measures. Thus, there is a pressing need to better understand how obesity increases (liver) cancer risk and mortality rate. Here, we addressed the hypothesis whether metabolism, which is a biological process that is important to sustain cancer proliferation, is the functional interconnection between obesity and liver cancer. To address this hypothesis, we exploited in vivo mouse models (to simulate obese versus lean physiology) and beyond state of the art techniques of metabolomics and 13C tracer analysis, which enables us to determine the in vivo liver metabolism. Using these techniques, we identified strong patterns of metabolic changes in the liver that are induced by obesity and have the potential to be important for liver cancer development and progression. Moreover, we identified a metabolic pathway novel to cancer cells that is associated with obesity. In conclusion, with our work we have increased the understanding of how diet induces liver cancer and we expect that this knowledge will contribute on the long term to an improved cancer treatment and preventative measures in obese patients. This Marie Curie Career Integration Grant support me in establishing an independent research group at the VIB Center for Cancer Biology. The success of my research and my expertise in metabolism (fostered through this grant) allowed a successful integration into VIB and Europe evident from multiple collaborations that resulted in high impact research published for example in Nature and Cell Metabolism. Moreover, my career is progressing as planed as I have advance from a junior PI to a full PI.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Continuous research on cancer has unraveled genetic alterations and subsequently signal transduction pathways changed in a cancer cell, thereby it emerged that many of the genetic factors commonly altered in cancer cells often target metabolic genes. An altered metabolism allows cancer cells to sustain their proliferative needs. Yet, whether altered metabolic fluxes and metabolite concentrations, which define the metabolic state of a cell, are only a consequence or can be a cause of cancer is a major question in the field. The hypothesis that certain metabolic states can precondition a cell for cancer is supported by epidemiological studies showing that patients suffering from diabetes or obesity have an increased risk to develop cancer and an increased cancer mortality rate.We propose to elucidate whether certain metabolic states promote liver cancer, which is in 30% of the cases associated with diabetes and obesity. We will measure metabolite concentrations and metabolic fluxes in tumorigenic versus non-malignant liver cells in vitro, to systematically identify metabolic states that are sufficient to drive an oncogenic transformation in the liver. Subsequently, we will map them in vivo onto metabolic states quantified in a diet and carcinogen induced mouse model, with the final goal to unravel the causal link between the increased liver cancer risk and the metabolic syndrome. Elucidating this metabolic interface will provide a mechanistic understanding of tumor initiating events in patients suffering from the metabolic syndrome. It will subsequently lead to new therapeutic strategies to prevent increased tumor events and cancer driven mortality rates in such patients.
Оригинален текст от CORDIS (на английски).
Участници
- VIB VZW · ZWIJNAARDE - GENTКоординаторБелгия
Връзки
Данни: CORDIS, © Европейски съюз