Ints6-flox Mouse

INTS6, also known as Deleted in cancer cells 1 (DICE1), is a subunit of the Integrator complex. This complex is involved in 3' end processing of small nuclear RNAs (snRNAs) and premature transcription termination of many protein-coding genes. INTS6 plays a role in regulating the activity of the Integrator complex, especially through its interaction with protein phosphatase 2A (PP2A), and is associated with pathways like cell cycle regulation and various cancer-related signaling pathways [1,3,4].

In colorectal cancer, INTS6 expression is increased, and its down-regulation induces G1/S-phase cell cycle arrest, suppressing cell growth, while over-expression has the opposite effect. It promotes cancer progression by activating AKT and ERK signaling [2].

In prostate cancer, exogenous re-expression of INTS6 in androgen-independent cell lines suppresses colony formation, arresting cells in the G1 phase, and is linked to Wnt signaling pathway regulation [5]. Also, in castration-resistant prostate cancer cells, activation of INTS6 by a promoter-targeted small RNA suppresses cell proliferation and motility by regulating β-catenin signaling [6].

In conclusion, INTS6 has a significant impact on cell cycle regulation and cancer-related signaling pathways. Its dysregulation is associated with the development and progression of colorectal and prostate cancers. Studies on INTS6, including those using loss-of-function models, help in understanding the molecular mechanisms of cancer development and may provide potential therapeutic targets.