Abstract
The prevalence and incidence of cancers has risen over the last decade. Available treatments have improved outcomes, yet mortality and morbidity remain high, creating an urgent demand for personalized and new therapy targets. Interferon induced transmembrane protein (IFITM3) is highly expressed in cancers and is a marker of poor prognosis. In this review, we discuss recent advances in IFITM3 biology, the regulatory pathways, and its function within cancer as part of immunity and maintaining stemness. Overexpression of IFITM3 is likely an indirect effect of ongoing inflammation, immune and cancer epithelial-to-mesenchymal (EMT) related pathways i.e., interferons, TGF-β, WNT/β-catenin, etc. However, IFITM3 also influences tumorigenic phenotypes, such as cell proliferation, migration and invasion. Furthermore, IFITM3 plays a key role in cancer growth and maintenance. Silencing of IFITM3 reduces these phenotypes. Therefore, targeting of IFITM3 will likely have implications for potential cancer therapies.
Highlights
Cancer was the second leading cause of mortality in 2018, resulting in 9.6 million deaths globally [1]
The aim of this review is to study existing literature to better understand the role of IFITM3 in tumors and the tumor microenvironment (TME) and to identify possible oncogenic and/or immunogenic roles for these proteins
IFITM3 has a multi-dimensional role and may join multiple signaling pathways that are responsible for oncogenesis and tumor progression
Summary
Cancer was the second leading cause of mortality in 2018, resulting in 9.6 million deaths globally [1]. Especially newer immunotherapies, cancer mortality has been reduced and survival has increased. Recent focuses in cancer research have been towards understanding the cell extrinsic mechanisms of the tumor microenvironment (TME) and towards exploiting these mechanisms to treat and gain tumor control. This is especially important with immunotherapy becoming a routine part of cancer treatment and as combinatorial treatments are being explored. IFN is generally considered a pathway that stimulates the immune response, but recent evidence indicates IFN signaling can lead to immunosuppression and assist tumor spreading [3, 4]
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