Tumor-Promoting Effects of the Transcriptional Regulator CUX1 in PanNET

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Introduction: Previously, we identified CUX1 as mediator of metastatic behaviour and poor differentiation in human insulinomas. CUX1 mediated tumor-promoting functions via enhancing proliferation, resistance to apoptosis and angiogenesis in-vitro and in-vivo.

Aim(s): In patients with non-functioning pancreatic neuroendocrine tumors (PanNETs), the role of CUX1 has to be elucidated.

Materials and methods: We analyzed expression of CUX1 in two large cohorts (n=34 and n=104) of non-functional PanNETs in treatment-naïve and pre-treated patients as well as in the RIP1Tag2 mouse model. To further assess the functional role of CUX1, profiling of DNA damage-, proliferation- and apoptosis-associated genes was performed in CUX1-modulated Bon-1 cells. Validation of regulated genes was performed in Bon-1 and QGP1 cells with knock-down and overexpression strategies. Statistical evaluation was performed with cox regression, log-rank and Fisher´s exact test.

Conference: 17th Annual ENETSConcerence (2020)

Presenting Author: Weißbach J

Authors: Weißbach J, Schmitz R, Haybäck J, Perren A, Blank A,

Keywords: CUX1, RIP1Tag2, DAPK1, Apoptosis, Tumor Progression,