Research Group Prof. Dr. Melek Canan Arkan
Diet, Energy Metabolism, and Cancer
Metabolic Derangements in Cancer
Cancer is marked by dysregulation of the signaling pathways that orchestrate proliferation, cell death, tumor-promoting inflammation, and bioenergetic pathways. Our studies focus on elucidating the host and tumor energy metabolism in pancreatic and intestinal cancer, delineating the critical alterations that take place during disease and therapy, and targeting the metabolic vulnerability of tumor cells genetically or pharmacologically in relevant preclinical models using; mouse and 3D organoids, which may have a diagnostic value and can impact therapy response.
Imaging in Cancer
Late-stage presentation, inaccessible diagnosis, and resistance to therapy represent the most common causes of increased mortality in cancer patients. Our studies aim at identifying reliable biomarkers for early detection, developing approaches that target defined changes during specific stages of tumor development, progression, and therapy for bioimaging using MRI-detectable smart probes.
Diet, Microbiome, Circadian clock & Cancer
Human gut is inhabited by billions of bacteria contributing majorly to the regulation of metabolic functions and immune homeostasis. Dynamics of microbial community is critical since microbiota composition and functional profiles shape susceptibility to cancer and response to therapy. Nutrition can directly or indirectly modulate microbiome and play a decisive role in disease outcome. Our studies aim at unravelling the impact of dietary intake on microbiota structure and function during cancer and therapy. We elucidate whether precision nutrition can pave the way for individual-based interventions in cancer by regulating microbiome.
The intricate connection between diet, microbiota, and cancer: A jigsaw puzzle.
Arkan MC. Semin Immunol. 2017 Aug;32:35-42. doi: 10.1016/j.smim.2017.08.009. Epub 2017 Sep 1. PMID: 28870704 Review.
Cancer: Fat and the fate of pancreatic tumours.
Arkan MC. Nature. 2016 Aug 11;536(7615):157-8. doi: 10.1038/nature19419. Epub 2016 Aug 3. PMID: 27487208
High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity.
Schulz MD, Atay C, Heringer J, Romrig FK, Schwitalla S, Aydin B, Ziegler PK, Varga J, Reindl W, Pommerenke C, Salinas-Riester G, Böck A, Alpert C, Blaut M, Polson SC, Brandl L, Kirchner T, Greten FR, Polson SW, Arkan MC. Nature. 2014 Oct 23;514(7523):508-12. doi: 10.1038/nature13398. Epub 2014 Aug 31. PMID: 25174708 Free PMC article.
Inflammation and mitochondrial fatty acid beta-oxidation link obesity to early tumor promotion.
Khasawneh J, Schulz MD, Walch A, Rozman J, Hrabe de Angelis M, Klingenspor M, Buck A, Schwaiger M, Saur D, Schmid RM, Klöppel G, Sipos B, Greten FR, Arkan MC. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3354-9. doi: 10.1073/pnas.0802864106. Epub 2009 Feb 10. PMID: 19208810
More Publications
IL-17RA signaling provides dual tumor-suppressor function during late-stage colorectal carcinogenesis
Immunity. 2025 Mar 11;58(3):701-715.e8. doi: 10.1016/j.immuni.2025.02.005. Epub 2025 Feb 28.
ABSTRACT
Expression of interleukin (IL)-17 family cytokines is associated…
Gut microbial carcinogen metabolism: another avenue to cancer
Signal Transduct Target Ther. 2024 Oct 28;9(1):297. doi: 10.1038/s41392-024-02015-8.
NO ABSTRACT
PMID:39468009 | PMC:PMC11519342 | DOI:10.1038/s41392-024-02015-8
Colon tumour cell death causes mTOR dependence by paracrine P2X4 stimulation
Nature. 2022 Dec;612(7939):347-353. doi: 10.1038/s41586-022-05426-1. Epub 2022 Nov 16.
ABSTRACT
Solid cancers exhibit a dynamic balance between cell death and…
IKKα Promotes Intestinal Tumorigenesis by Limiting Recruitment of M1-like Polarized Myeloid Cells
Cell Rep. 2022 Mar 1;38(9):110471. doi: 10.1016/j.celrep.2022.110471.
NO ABSTRACT
PMID:35235803 | DOI:10.1016/j.celrep.2022.110471
Inflammatory fibroblasts mediate resistance to neoadjuvant therapy in rectal cancer
Cancer Cell. 2022 Feb 14;40(2):168-184.e13. doi: 10.1016/j.ccell.2022.01.004. Epub 2022 Feb 3.
ABSTRACT
Standard cancer therapy targets tumor cells without considering…
Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis
Cell. 2018 Jun 28;174(1):88-101.e16. doi: 10.1016/j.cell.2018.05.028. Epub 2018 Jun 14.
ABSTRACT
In colorectal cancer patients, a high density of cytotoxic CD8+ T cells…
The intricate connection between diet, microbiota, and cancer: A jigsaw puzzle
Semin Immunol. 2017 Aug;32:35-42. doi: 10.1016/j.smim.2017.08.009. Epub 2017 Sep 1.
ABSTRACT
The microbial community has a decisive role in determining our health and…
Cancer: Fat and the fate of pancreatic tumours
Nature. 2016 Aug 11;536(7615):157-8. doi: 10.1038/nature19419. Epub 2016 Aug 3.
NO ABSTRACT
PMID:27487208 | DOI:10.1038/nature19419
High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity
Nature. 2014 Oct 23;514(7523):508-12. doi: 10.1038/nature13398. Epub 2014 Aug 31.
ABSTRACT
Several features common to a Western lifestyle, including obesity and low…
IKKα promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells
Cell Rep. 2014 Jun 26;7(6):1914-25. doi: 10.1016/j.celrep.2014.05.006. Epub 2014 May 29.
ABSTRACT
The recruitment of immune cells into solid tumors is an essential…
Loss of acinar cell IKKα triggers spontaneous pancreatitis in mice
J Clin Invest. 2013 May;123(5):2231-43. doi: 10.1172/JCI64498. Epub 2013 Apr 8.
ABSTRACT
Chronic pancreatitis is an inflammatory disease that causes progressive…
Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties
Cell. 2013 Jan 17;152(1-2):25-38. doi: 10.1016/j.cell.2012.12.012. Epub 2012 Dec 27.
ABSTRACT
Cell-type plasticity within a tumor has recently been suggested to cause a…
Lymphotoxin β receptor signaling promotes development of autoimmune pancreatitis
Gastroenterology. 2012 Nov;143(5):1361-1374. doi: 10.1053/j.gastro.2012.07.112. Epub 2012 Aug 2.
ABSTRACT
BACKGROUND & AIMS: Little is known about the pathogenic…
IkappaBbeta is an essential co-activator for LPS-induced IL-1beta transcription in vivo
J Exp Med. 2010 Nov 22;207(12):2621-30. doi: 10.1084/jem.20100864. Epub 2010 Oct 25.
ABSTRACT
Inhibitor of κB (IκB) β (IκBβ) represents one of the major primary…
IKK- and NF-κB-mediated functions in carcinogenesis
Curr Top Microbiol Immunol. 2011;349:159-69. doi: 10.1007/82_2010_97.
ABSTRACT
Since the initial cloning of RelA and its close relationship to c-Rel, the cellular…
Ink4a/Arf and oncogene-induced senescence prevent tumor progression during alternative colorectal tumorigenesis
Cancer Cell. 2010 Aug 9;18(2):135-46. doi: 10.1016/j.ccr.2010.06.013.
ABSTRACT
Colonic cancers with a serrated morphology have been proposed to comprise a molecularly…
Inflammation and mitochondrial fatty acid beta-oxidation link obesity to early tumor promotion
Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3354-9. doi: 10.1073/pnas.0802864106. Epub 2009 Feb 10.
ABSTRACT
Obesity is associated with increased risk for developing…
gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis
Cancer Cell. 2009 Feb 3;15(2):91-102. doi: 10.1016/j.ccr.2009.01.002.
ABSTRACT
Although gastrointestinal cancers are frequently associated with chronic inflammation, the…
Opposing functions of IKKbeta during acute and chronic intestinal inflammation
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15058-63. doi: 10.1073/pnas.0808216105. Epub 2008 Sep 24.
ABSTRACT
NF-kappaB is a key transcriptional regulator of…
NF-kappaB is a negative regulator of IL-1beta secretion as revealed by genetic and pharmacological inhibition of IKKbeta
Cell. 2007 Sep 7;130(5):918-31. doi: 10.1016/j.cell.2007.07.009.
ABSTRACT
IKKbeta-dependent NF-kappaB activation plays a key role in innate immunity and inflammation,…
Differential regulation of hepatic transporters in the absence of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and nuclear factor-kappaB in two models of cholestasis
Drug Metab Dispos. 2007 Mar;35(3):402-9. doi: 10.1124/dmd.106.012138. Epub 2006 Dec 6.
ABSTRACT
Hepatic transporters are responsible for uptake and efflux of bile acids…
IKK-beta links inflammation to obesity-induced insulin resistance
Nat Med. 2005 Feb;11(2):191-8. doi: 10.1038/nm1185. Epub 2005 Jan 30.
ABSTRACT
Inflammation may underlie the metabolic disorders of insulin resistance and type 2…
Physiological amounts of ascorbate potentiate phorbol ester-induced nuclear-binding of AP-1 transcription factor in cells of macrophagic lineage
Free Radic Biol Med. 2001 Aug 1;31(3):374-82. doi: 10.1016/s0891-5849(01)00601-3.
ABSTRACT
The aim of the reported research was to assess the potential modulatory effect…
Up-regulation of the fibrogenic cytokine TGF-beta1 by oxysterols: a mechanistic link between cholesterol and atherosclerosis
FASEB J. 2001 Jul;15(9):1619-21. doi: 10.1096/fj.00-0668fje.
NO ABSTRACT
PMID:11427505 | DOI:10.1096/fj.00-0668fje
Lipid oxidation products in cell signaling
Free Radic Biol Med. 2000 May 1;28(9):1370-8. doi: 10.1016/s0891-5849(00)00216-1.
ABSTRACT
The recent research on the impact that oxidative changes of biolipids could…
Jobs
Call for Medical Students Thesis Opportunity in Microbiome Research
Our research lab is seeking motivated and curious medical students to conduct thesis study focused on microbiome research. We…
Call for Bachelor and Master Students - Thesis Opportunity in Microbiome Research
We are seeking motivated and curious students to conduct Bachelor and Master thesis study focused on microbiome research. We…
Ph.D. Position in Microbiome, Cancer, and Circadian Rhythm Research
This fully-funded PhD position by the FCI focuses on exploring how the human microbiome interacts with circadian biology to…












