Aerobic glycolysis is critical for tumor growth and metastasis. Previously, we have found that the overexpression of the inhibitor of growth 5 (ING5) inhibits lung cancer aggressiveness and epithelial–mesenchymal transition (EMT). However, whether ING5 regulates lung cancer metabolism reprogramming remains unknown. Here, by quantitative proteomics, we showed that ING5 differentially regulates protein phosphorylation and identified a new site (Y163) of the key glycolytic enzyme PDK1 whose phosphorylation was upregulated 13.847-fold. By clinical study, decreased p-PDK1Y163 was observed in lung cancer tissues and correlated with poor survival. p-PDK1Y163 represents the negative regulatory mechanism of PDK1 by causing PDHA1 dephosphorylation and activation, leading to switching from glycolysis to oxidative phosphorylation, with increasing oxygen consumption and decreasing lactate production. These effects could be impaired by PDK1Y163F mutation, which also impaired the inhibitory effects of ING5 on cancer cell EMT and invasiveness. Mouse xenograft models confirmed the indispensable role of p-PDK1Y163 in ING5-inhibited tumor growth and metastasis. By siRNA screening, ING5-upregulated TIE1 was identified as the upstream tyrosine protein kinase targeting PDK1Y163. TIE1 knockdown induced the dephosphorylation of PDK1Y163 and increased the migration and invasion of lung cancer cells. Collectively, ING5 overexpression—upregulated TIE1 phosphorylates PDK1Y163, which is critical for the inhibition of aerobic glycolysis and invasiveness of lung cancer cells.

Much of our knowledge of the protein PD-1, a leading cancer treatment target, comes from studies in mice. In a comprehensive assessment of PD-1, researchers have found that PD-1 in mice is significantly weaker than the human version, providing new information on how cancer treatments are developed.

For many nursing home residents, a trip to the hospital can be a jarring experience — one that leaves them confused and stressed. Yet avoidable transfers happen far too often, not only disrupting a resident’s routine but also costing the U.S. healthcare system $2.6 billion annually.

When researchers at the University of Missouri recently looked at the decision-making process for whether or not to transfer nursing home residents to the hospital, they quickly discovered that it’s complicated — particularly for residents with cognitive impairment who may not be able to communicate their preferences.