LAUSR

Simple Summary In this review article, we will deepen the topic of cancer cell communication with the surrounding non-cancerous cells. In particular, the non-mutational events that modified gene expression, namely “epigenetics”, involved in cell–cell interaction will be the center of this work. Many studies have described the mechanism of back-and-forth communication between cancer and stromal cells, and very recent studies suggested that epigenetics may play an important role in this setting. This work will describe recent advances in the field of epigenetic mechanisms involved in tumour–stroma crosstalk. Understanding these processes can be useful in future cancer therapy design. Abstract Despite cancer having been usually considered the result of genetic mutations, it is now well established that epigenetic dysregulations play pivotal roles in cancer onset and progression. Hence, inactivation of tumour suppressor genes can be gained not only by genetic mutations, but also by epigenetic mechanisms such as DNA methylation and histone modifications. To occur, epigenetic events need to be triggered by genetic alterations of the epigenetic regulators, or they can be mediated by intracellular and extracellular stimuli. In this last setting, the tumour microenvironment (TME) plays a fundamental role. Therefore, to decipher how epigenetic changes are associated with TME is a challenge still open. The complex signalling between tumour cells and stroma is currently under intensive investigation, and most of the molecules and pathways involved still need to be identified. Neoplastic initiation and development are likely to involve a back-and-forth crosstalk among cancer and stroma cells. An increasing number of studies have highlighted that the cancer epigenome can be influenced by tumour microenvironment and vice versa. Here, we discuss about the recent literature on tumour–stroma interactions that focus on epigenetic mechanisms and the reciprocal regulation between cancer and TME cells.