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Glucose starvationinducesLKB1-AMPK-mediatedMMP-9 expression incancer cells Hitoshi EndoSatoshi OwadaYutaka Inagaki2018 год

Glucose starvation induces LKB1-AMPK-mediated MMP-9 expression in cancer cells
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Аннотация: Abstract Cancer cells utilise the glycolytic pathway to support their rapid growth and proliferation. Since cells in most solid tumours are subjected to severe microenvironmental stresses including low nutrient and oxygen availability, such cancer cells must develop mechanisms to overcome these unfavourable growth conditions by metabolic adaptation. Although the liver kinase B1 (LKB1)-adenosine monophosphate-activated kinase (AMPK) signalling pathway plays a pivotal role in maintaining energy homeostasis under conditions of metabolic stress, the role of LKB1-AMPK signalling in aiding cancer cell survival and in malignant tumours has not yet been fully elucidated. We show that glucose starvation promotes cancer cell invasiveness and migration through LKB1-AMPK-regulated MMP-9 expression. Most intriguingly, triggering the LKB1-AMPK signalling pathway by glucose starvation-induced oxidative stress facilitates selective autophagy, which in turn enhances Keap1 degradation and the subsequent activation of Nrf2. Following this, Nrf2 regulates the transactivation of MMP-9 via Nrf2 binding sites in the promoter region of the MMP-9 gene. These mechanisms also contribute to the suppression of excessive oxidative stress under glucose starvation, and protect against cell death. Our data clearly shows that LKB1-AMPK signalling not only maintains energy and oxidative stress homeostasis, but could also promote cancer progression during metabolic stress conditions by MMP-9 induction.
Год издания: 2018
Авторы: Hitoshi Endo, Satoshi Owada, Yutaka Inagaki, Yukari Shida, Masayuki Tatemichi
Издательство: Nature Portfolio
Источник: Scientific Reports
Ключевые слова: Metabolism, Diabetes, and Cancer, Autophagy in Disease and Therapy, FOXO transcription factor regulation
Другие ссылки: Scientific Reports (PDF)
Scientific Reports (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)