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Catalytic-independent and subtype-specific roles of fructose-1,6- bisphosphatase 2 in sarcoma growth Bailey Nance

Dissertations & Theses @ University of Pennsylvania Available online

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Format:
Book
Thesis/Dissertation
Author/Creator:
Nance, Bailey, author.
Contributor:
University of Pennsylvania. Cell and Molecular Biology., degree granting institution.
Language:
English
Subjects (All):
Cellular biology.
Physiology.
Molecular biology.
Biochemistry.
0379.
0487.
0307.
0719.
Local Subjects:
Cellular biology.
Physiology.
Molecular biology.
Biochemistry.
0379.
0487.
0307.
0719.
Genre:
Academic theses
Physical Description:
1 online resource (109 pages)
Contained In:
Dissertations Abstracts International 87-12B
Place of Publication:
Ann Arbor : ProQuest Dissertations and Theses, 2026
Language Note:
English
Summary:
Fructose-1,6-bisphosphatase 2 (FBP2), a rate limiting gluconeogenic enzyme, is primarily expressed in skeletal muscle yet its physiological contribution in this tissue is not fully established. To investigate its function, we examined FBP2 expression in different skeletal muscle fiber types and in myogenic progenitor populations. Using immunohistochemical and transcriptomic analyses, we show that FBP2 is selectively expressed in fast-twitch skeletal muscle fibers and is absent in myogenic progenitors. Ectopic FBP2 expression in myoblasts impairs differentiation and reduces mitochondrial mass, suggesting that FBP2 must be temporally restricted for myogenesis.FBP2 also has emerging roles in sarcoma malignancy. Altered cancer metabolism influences tumor growth through both enzymatic and non-enzymatic mechanisms; however, FBP2's catalytic activity-independent functions are not fully defined. Here, we demonstrate that FBP2 exerts subtype-specific effects on sarcoma growth through both catalytically activity-dependent and -independent mechanisms. Ectopic expression of wildtype or a novel catalytically inactive FBP2 mutant (E98A) suppresses proliferation and tumor growth in liposarcoma and fibrosarcoma models in vitro and in vivo. In contrast, FBP2 appears to promote tumor growth in an autochthonous LSL-KrasG12D/+;Trp53fl/fl (KP) model of undifferentiated pleiomorphic sarcoma (UPS), reflecting human epidemiological data. Collectively, these findings reveal FBP2 as a context-dependent regulator of metabolic signaling and sarcoma progression, highlighting its potential as a prognostic biomarker in STS
Notes:
Source: Dissertations Abstracts International, Volume: 87-12, Section: B.
Advisors: Simon, M. Celeste; Chou, Margaret M. Committee members: Arany, Zoltan P.; Blobel, Gerd A.; Mourkioiti, Foteini
Ph.D. University of Pennsylvania 2026
Vendor supplied data
Local Notes:
School code: 0175
ISBN:
9798247980735
Access Restriction:
Restricted for use by site license

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