RABL6A Promotes Pancreatic Neuroendocrine Tumor Angiogenesis and Progression In Vivo.

Autor:	Maharjan CK; Department of Neuroscience and Pharmacology, The University of Iowa, Iowa City, IA 52242, USA., Umesalma S; Department of Neuroscience and Pharmacology, The University of Iowa, Iowa City, IA 52242, USA., Kaemmer CA; Department of Neuroscience and Pharmacology, The University of Iowa, Iowa City, IA 52242, USA., Muniz VP; Department of Neuroscience and Pharmacology, The University of Iowa, Iowa City, IA 52242, USA., Bauchle C; Fraternal Order of Eagles Diabetes Research Center, The University of Iowa, Iowa City, IA 52242, USA., Mott SL; Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USA., Zamba KD; Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USA.; Department of Biostatistics, The University of Iowa, Iowa City, IA 52242, USA., Breheny P; Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USA.; Department of Biostatistics, The University of Iowa, Iowa City, IA 52242, USA., Leidinger MR; Department of Pathology, The University of Iowa, Iowa City, IA 52242, USA., Darbro BW; Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USA.; Department of Pediatrics, The University of Iowa, Iowa City, IA 52242, USA., Stephens SB; Fraternal Order of Eagles Diabetes Research Center, The University of Iowa, Iowa City, IA 52242, USA., Meyerholz DK; Department of Pathology, The University of Iowa, Iowa City, IA 52242, USA., Quelle DE; Department of Neuroscience and Pharmacology, The University of Iowa, Iowa City, IA 52242, USA.; Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USA.; Department of Pathology, The University of Iowa, Iowa City, IA 52242, USA.
Jazyk:	angličtina
Zdroj:	Biomedicines [Biomedicines] 2021 Jun 02; Vol. 9 (6). Date of Electronic Publication: 2021 Jun 02.
DOI:	10.3390/biomedicines9060633
Abstrakt:	Pancreatic neuroendocrine tumors (pNETs) are difficult-to-treat neoplasms whose incidence is rising. Greater understanding of pNET pathogenesis is needed to identify new biomarkers and targets for improved therapy. RABL6A, a novel oncogenic GTPase, is highly expressed in patient pNETs and required for pNET cell proliferation and survival in vitro. Here, we investigated the role of RABL6A in pNET progression in vivo using a well-established model of the disease. RIP-Tag2 (RT2) mice develop functional pNETs (insulinomas) due to SV40 large T-antigen expression in pancreatic islet β cells. RABL6A loss in RT2 mice significantly delayed pancreatic tumor formation, reduced tumor angiogenesis and mitoses, and extended survival. Those effects correlated with upregulation of anti-angiogenic p19ARF and downregulation of proangiogenic c-Myc in RABL6A-deficient islets and tumors. Our findings demonstrate that RABL6A is a bona fide oncogenic driver of pNET angiogenesis and development in vivo.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu