Mitochondrial dynamics links PINCH-1 signaling to proline metabolic reprogramming and tumor growth

Proline metabolism is critical for cellular response to microenvironmental stress in living organisms across different kingdoms, ranging from bacteria, plants to animals. In bacteria and plants, proline is known to accrue in response to osmotic and other stresses. In higher organisms such as human, proline metabolism plays important roles in physiology as well as pathological processes including cancer. The importance of proline metabolism in physiology and diseases lies in the fact that the products of proline metabolism are intimately involved in essential cellular processes including protein synthesis, energy production and redox signaling. A surge of protein synthesis in fast proliferating cancer cells, for example, results in markedly increased demand for proline. Proline synthesis is frequently unable to meet the demand in fast proliferating cancer cells. The inadequacy of proline or “proline vulnerability” in cancer may provide an opportunity for therapeutic control of cancer progression. To this end, it is important to understand the signaling mechanism through which proline synthesis is regulated. In a recent study (Guo et al., Nat Commun 11(1):4913, doi: 10.1038/s41467-020-18753-6), we have identified PINCH-1, a component of cell-extracellular matrix (ECM) adhesions, as an important regulator of proline synthesis and cancer progression.