title: Reprogramming of Basic Cellular Metabolism by  Vitamin D in Tumor Cells
creator: Abouelmaaty Abdelgawad, Mohamed
subject: ddc-570
subject: 570 Life sciences
description: Recent years have witnessed a resurgence in tumor metabolism research. Cancer cells are  known to exhibit multiple distinct aberrations in energy-utilization that help them sustain rapid  growth and proliferation, as well as cope with harsh microenvironment conditions, such as  limited nutrient availability and oxygenation. Amplified growth factor and oncogenic signaling  have been implicated in the observed metabolic reprogramming in cancers, and thus, drugs that  target these signaling aberrations have also been shown to impact metabolism. Furthermore,  several drugs have been developed or repurposed to interfere with metabolic processes in  transformed cells. In this thesis, the results of my investigations into the ability of 1,25-  dihydroxyvitamin D3 [1,25(OH)2D3] (also referred to as calcitriol)—the hormonally active  form of vitamin D3—to influence metabolic pathways in different cancer models are presented.  Using prostate cancer cell lines with different androgen sensitivities, as well as breast cancer  cell lines representing different molecular subtypes, it is shown that 1,25(OH)2D3 is a major  regulator of energy-utilization and glucose-sensing networks in these cancer cells. Detailed  investigation of cellular metabolism using biosensor technology, GC/MS-based metabolomics,  RT-qPCR gene expression analyses, enzymatic activity assays, FACS analyses, and  immunoblotting, illustrates that 1,25(OH)2D3 induces global rewiring of glucose-metabolizing  pathways, as well as modulates energy-related signaling molecules including AMP-activated  protein kinase and thioredoxin-interacting protein (TXNIP). My results also show, that in  contrast to the long-standing association between TXNIP and calcitriol, the former is not  universally regulated by the latter in cancer cell lines of various tissue origins, and that the  canonical regulation is subject to glucose-availability. In conclusion, I like to propose that  regulation of onco-metabolism is a mechanism through which calcitriol induces its anti-cancer  effects, and argue that continued investigations into this theme would elucidate ways to improve  the molecule’s therapeutic potential.
date: 2018
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/24829/1/PhD%20thesis_MA%20Abu%20el%20Maaty_Final%20version.pdf
identifier: DOI:10.11588/heidok.00024829
identifier: urn:nbn:de:bsz:16-heidok-248295
identifier:   Abouelmaaty Abdelgawad, Mohamed  (2018) Reprogramming of Basic Cellular Metabolism by Vitamin D in Tumor Cells.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/24829/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng