Abstract 3512: MYCN and survivin cooperatively contribute to malignant transformation of fibroblasts

The oncogenes MYCN and survivin (BIRC5) maintain aggressiveness of diverse cancers including sarcomas. To investigate whether these oncogenes cooperate in initial malignant transformation, we transduced them into Rat-1 fibroblasts. Indeed, survivin enhanced MYCN-driven contact-uninhibited and anchorage-independent growth in vitro. Importantly, upon subcutaneous transplantation into mice, cells overexpressing both instead of either one of the oncogenes generated tumors with shortened latency, marked anaplasia and an increased proliferation-to-apoptosis ratio resulting in accelerated growth. Mechanistically, the increased tumorigenicity was associated with an enhanced Warburg effect and HIF1α-linked vascular remodeling. This cooperation between MYCN and survivin may be important in the genesis of several cancers. Citation Format: Nora Hipp, Lisa Christner, Thomas Wirth, Wolfgang Mueller-Klieser, Stefan Walenta, Evelin Schrock, Klaus-Michael Debatin, Christian Beltinger. MYCN and survivin cooperatively contribute to malignant transformation of fibroblasts. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3512. doi:10.1158/1538-7445.AM2014-3512