PTEN and lung adenocarcinoma: Under the condition of hypoxia, NOTCH1 can be activated by HIF1α (hypoxia-inducible factor 1-α) in lung adenocarcinoma cells (e.g., A549 cells), and the activated NOTCH1 suppressed the expression of PTEN (phosphatase and tensin homolog) and increased the expression of IGF-1R (insulin growth factor 1 receptor) to activate AKT (also known as protein kinase B), which in turn inhibited cell death and promoted cell growth [15].