RAP1/TERF2IP—A Multifunctional Player in Cancer Development

SIMPLE SUMMARY: RAP1 (TERF2IP) is a member of the shelterin complex that protects telomeric DNA and plays a critical role in maintaining chromosome stability. However, mammalian RAP1 was recently found to have additional functions apart from telomeres, acting as a regulator of the NF-κB pathway and transcription factor, and has been suggested that they have putative roles in cancer development. Here, we focus on the main roles of RAP1 in different mechanisms of oncogenesis, progression, and chemoresistance, and consider the clinical significance of findings about its regulation and biological functions. ABSTRACT: Mammalian RAP1 (TERF2IP), the most conserved shelterin component, plays a pleiotropic role in the regulation of a variety of cellular processes, including cell metabolism, DNA damage response, and NF-κB signaling, beyond its canonical telomeric role. Moreover, it has been demonstrated to be involved in oncogenesis, progression, and chemoresistance in human cancers. Several mutations and different expression patterns of RAP1 in cancers have been reported. However, the functions and mechanisms of RAP1 in various cancers have not been extensively studied, suggesting the necessity of further investigations. In this review, we summarize the main roles of RAP1 in different mechanisms of cancer development and chemoresistance, with special emphasis on the contribution of RAP1 mutations, expression patterns, and regulation by non-coding RNA, and briefly discuss telomeric and non-telomeric functions.