RABL6A Promotes Pancreatic Neuroendocrine Tumor Angiogenesis and Progression In Vivo

Chandra K Maharjan; Shaikamjad Umesalma; Courtney A Kaemmer; Viviane P Muniz; Casey Bauchle; Sarah L Mott; K. D Zamba; Patrick Breheny; Mariah R Leidinger; Benjamin W Darbro; Samuel B Stephens; David K Meyerholz; Dawn E Quelle

doi:10.3390/biomedicines9060633

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RABL6A Promotes Pancreatic Neuroendocrine Tumor Angiogenesis and Progression In Vivo

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RABL6A Promotes Pancreatic Neuroendocrine Tumor Angiogenesis and Progression In Vivo

Chandra K Maharjan, Shaikamjad Umesalma, Courtney A Kaemmer, Viviane P Muniz, Casey Bauchle, Sarah L Mott, K. D Zamba, Patrick Breheny, Mariah R Leidinger, Benjamin W Darbro, …

Biomedicines, Vol.9(6), p.633

06/02/2021

DOI: 10.3390/biomedicines9060633

PMCID: PMC8228095

PMID: 34199469

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Abstract

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.

Details

Title: Subtitle: RABL6A Promotes Pancreatic Neuroendocrine Tumor Angiogenesis and Progression In Vivo
Creators: Chandra K Maharjan - University of Iowa
Shaikamjad Umesalma - University of Iowa
Courtney A Kaemmer - University of Iowa
Viviane P Muniz - University of Iowa
Casey Bauchle - University of Iowa
Sarah L Mott - University of Iowa
K. D Zamba - University of Iowa
Patrick Breheny - University of Iowa
Mariah R Leidinger - University of Iowa
Benjamin W Darbro - University of Iowa
Samuel B Stephens - University of Iowa
David K Meyerholz - University of Iowa
Dawn E Quelle - University of Iowa
Resource Type: Journal article
Publication Details: Biomedicines, Vol.9(6), p.633
DOI: 10.3390/biomedicines9060633
PMID: 34199469
PMCID: PMC8228095
NLM abbreviation: Biomedicines
ISSN: 2227-9059
eISSN: 2227-9059
Grant note: DOI: 10.13039/100000054, name: National Cancer Institute, award: NET SPORE P50 CA174521, Core Grant P30 CA086862
Language: English
Date published: 06/02/2021
Academic Unit: Radiology; Stead Family Department of Pediatrics; Pathology; Biostatistics; Medical Genetics and Genomics; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984186412302771

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