Remembrance of dead cells past: discovering that the extracellular matrix is a cell survival factor

In 1992, Jere Meredith and I followed up on a serendipitous observation and showed that matrix deprivation can lead to apoptosis. Our article in Molecular Biology of the Cell, together with work form Steve Frisch's lab, helped establish the paradigm that integrin signals control cell survival in a variety of systems. It has been a pleasure to watch that work take on a life of its own as other investigators have explored its role in processes such as cavitation, regression of the mammary gland at the end of pregnancy, cancer metastasis, and tumor resistance to chemotherapy. Recently, we described an exception to the paradigm: In some tumors, reagents that activate integrin signaling enhance apoptosis in response to chemotherapy.