Adaptive Stress Responses During Tumor Metastasis and Dormancy

To survive inhospitable environments, tumor cells are forced to remodel their signaling pathways by altering transcription, translation, and post-translational modifications. This adaptation is regulated in a spatial and temporal manner and gives rise to individual tumor cells with distinct gene expression and metabolic signatures. Such phenotypic heterogeneity is the result of tumor cell plasticity, which–together with the genetic background of the tumor–determines whether cells resist environmental stress, enter dormancy, or metastasize. This review summarizes our understanding of how tumor cells exploit the cellular stress response to balance proliferation, differentiation, and survival signals, as well as to remodel local and distant environments. We focus in particular on tumor metastasis, which is the greatest impediment to clinical management of cancers today.