How the interplay among the tumor microenvironment and the gut microbiota influences the stemness of colorectal cancer cells

Abstract

Colorectal cancer (CRC) remains the third most prevalent cancer disease andinvolves a multi-step process in which intestinal cells acquire malignant characteri-stics. It is well established that the appearance of distal metastasis in CRCpatients is the cause of a poor prognosis and treatment failure. Nevertheless, inthe last decades, CRC aggressiveness and progression have been attributed to aspecific cell population called CRC stem cells (CCSC) with features like tumorinitiation capacity, self-renewal capacity, and acquired multidrug resistance.Emerging data highlight the concept of this cell subtype as a plastic entity that hasa dynamic status and can be originated from different types of cells throughgenetic and epigenetic changes. These alterations are modulated by complex anddynamic crosstalk with environmental factors by paracrine signaling. It is knownthat in the tumor niche, different cell types, structures, and biomolecules coexistand interact with cancer cells favoring cancer growth and development. Together,these components constitute the tumor microenvironment (TME). Most recently,researchers have also deepened the influence of the complex variety of microorganisms that inhabit the intestinal mucosa, collectively known as gut microbiota,on CRC. Both TME and microorganisms participate in inflammatory processesthat can drive the initiation and evolution of CRC. Since in the last decade, crucialadvances have been made concerning to the synergistic interaction among theTME and gut microorganisms that condition the identity of CCSC, the dataexposed in this review could provide valuable insights into the biology of CRCand the development of new targeted therapies.