Trop2: From development to disease

Background: Trop2 was first discovered as a biomarker of invasive trophoblast cells. Since then most research has focused on its role in tumourigenesis because it is highly expressed in the vast majority of human tumours and animal models of cancer. It is also highly expressed in stem cells and in many organs during development. Results: We review the multifaceted role of Trop2 during development and tumourigenesis, including its role in regulating cell proliferation and migration, self‐renewal, and maintenance of basement membrane integrity. We discuss the evolution of Trop2 and its related protein Epcam (Trop1), including their distinct roles. Mutation of Trop2 leads to gelatinous drop‐like corneal dystrophy, whereas over‐expression of Trop2 in human tumours promotes tumour aggressiveness and increases mortality. Although Trop2 expression is sufficient to promote tumour growth, the surprising discovery that Trop2‐null mice have an increased risk of tumour development has highlighted the complexity of Trop2 signaling. Recently, studies have begun to identify the mechanisms underlying TROP2's functions, including regulated intramembrane proteolysis or specific interactions with integrin β1 and claudin proteins. Conclusions: Understanding the mechanisms underlying TROP2 signaling will clarify its role during development, aid in the development of better cancer treatments and unlock a promising new direction in regenerative medicine. Developmental Dynamics 244:99–109, 2015. © 2014 Wiley Periodicals, Inc. Key Findings Our manuscript comprehensively reviews the current literature regarding Trop2 and to our knowledge, is the only review covering the diverse roles of Trop2 in organogenesis, cancer and stem cell biology. It also integrates the recent studies examining the mechanisms of Trop2 signalling and to our knowledge provides the first schematic diagram showing all known and postulated mechanisms by which Trop2 mediates it's effects. The review also compares the known roles of Trop2 with that of the only other Trop2 protein family member, EpCAM (Trop1; a well‐known marker of stem cells), demonstrating evidence for a divergence in their roles.