Ccdc137-KO Mouse

CCDC137, a member of the coiled-coil domain containing (CCDC) family, is involved in multiple biological processes. It has been associated with important signaling pathways such as the β-catenin and AKT pathways [1,3]. In the context of diseases, it is significantly linked to cancer development and progression, playing a potential oncogenic role [1,3,4,5,7].

In hepatocellular carcinoma (HCC), elevated CCDC137 expression correlates with poor prognosis. It promotes HCC progression both in vitro and in vivo. Mechanistically, CCDC137 binds to LZTS2, a negative regulator of β-catenin, facilitating its K48-linked poly-ubiquitination via recruiting E3 ubiquitin ligase β-TrCP in the nucleus, thus activating the AKT and β-catenin pathways [1]. Also, CCDC137 binds to FOXM1, JTV1, LASP1, and FLOT2 mRNAs, increasing their cytoplasmic localization to enhance protein expressions, which in turn activates AKT signaling to promote HCC [3].

In colorectal cancer, CDK12 regulates the transcription of CCDC137, which is associated with hepatic metastasis [2]. Pan-cancer analysis shows that CCDC137 is over-expressed in various tumor types, associated with worse survival, and may contribute to an immunosuppressive tumor microenvironment [4].

In lung adenocarcinoma, CCDC137 was initially reported to be part of an oncogenic axis with CPSF1, though the related study was later retracted [7,8]. Additionally, in breast cancer, CCDC137 transcripts were found to contain a non-synonymous RNA variant unique to cancer tissue compared to adjacent normal tissue [9]. HIV-1 Vpr can deplete CCDC137, causing G2/M cell-cycle arrest and enhancing viral gene expression [6].

In conclusion, CCDC137 plays a crucial role in cancer-related biological processes, especially in HCC, colorectal cancer, and potentially in other cancer types. Its involvement in key signaling pathways makes it a potential therapeutic target. The studies on CCDC137, including those from in vitro and in vivo models, help in understanding its role in disease development, offering insights for developing targeted therapies against related cancers.