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.

Team

Prof. Dr. Canan Arkan

Prof. Dr. Canan Arkan

Research Group Leader

Placeholder Image

Asude Callak Kirisözü

Doctoral Researcher

Alan Guichard

Alan Guichard

Research Technician

Zeynep Sena Karahan

Zeynep Sena Karahan

Doctoral Researcher

Angeles Macias Pardo

Angeles Macias Pardo

Labmanager/Research Assistant

Selected Publications

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 

  • Dominic Denk
  • Mallika Ramakrishnan
  • Claire Conche
  • Charles Pallangyo
  • Marina Pesic
  • Fatih Ceteci
  • Kilian B Kennel
  • Asude C Kirisözü
  • Esther Engel
  • Kathleen Mohs
  • Birgit Ritter
  • Angeles Macias Pardo
  • Ezgi Özkurt
  • Falk Hildebrand
  • Ari Waisman
  • Melek C Arkan
  • Florian R Greten

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…

  • Florian R Greten
  • Melek C Arkan

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

  • Mark Schmitt
  • Fatih Ceteci
  • Jalaj Gupta
  • Marina Pesic
  • Tim W Böttger
  • Adele M Nicolas
  • Kilian B Kennel
  • Esther Engel
  • Matthias Schewe
  • Asude Callak Kirisözü
  • Valentina Petrocelli
  • Yasamin Dabiri
  • Julia Varga
  • Mallika Ramakrishnan
  • Madina Karimova
  • Andrea Ablasser
  • Toshiro Sato
  • Melek C Arkan
  • Frederic J de Sauvage
  • Florian R Greten

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…

  • Serkan I Göktuna
  • Ozge Canli
  • Julia Bollrath
  • Alexander A Fingerle
  • David Horst
  • Michaela A Diamanti
  • Charles Pallangyo
  • Moritz Bennecke
  • Tim Nebelsiek
  • Arun K Mankan
  • Roland Lang
  • David Artis
  • Yinling Hu
  • Thomas Patzelt
  • Jürgen Ruland
  • Thomas Kirchner
  • M Mark Taketo
  • Alain Chariot
  • Melek C Arkan
  • Florian R Greten

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

  • Adele M Nicolas
  • Marina Pesic
  • Esther Engel
  • Paul K Ziegler
  • Markus Diefenhardt
  • Kilian B Kennel
  • Florian Buettner
  • Claire Conche
  • Valentina Petrocelli
  • Eiman Elwakeel
  • Andreas Weigert
  • Anna Zinoveva
  • Maximilian Fleischmann
  • Björn Häupl
  • Cem Karakütük
  • Hanibal Bohnenberger
  • Mohammed H Mosa
  • Lars Kaderali
  • Jochen Gaedcke
  • Michael Ghadimi
  • Franz Rödel
  • Melek C Arkan
  • Thomas Oellerich
  • Claus Rödel
  • Emmanouil Fokas
  • Florian R Greten

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…

  • Paul K Ziegler
  • Julia Bollrath
  • Charles K Pallangyo
  • Takaji Matsutani
  • Özge Canli
  • Tiago De Oliveira
  • Michaela A Diamanti
  • Nina Müller
  • Jaba Gamrekelashvili
  • Tracy Putoczki
  • David Horst
  • Arun K Mankan
  • Meryem G Öner
  • Susanna Müller
  • Josef Müller-Höcker
  • Thomas Kirchner
  • Julia Slotta-Huspenina
  • M Mark Taketo
  • Thomas Reinheckel
  • Stefan Dröse
  • Andrew C Larner
  • Winfried S Wels
  • Matthias Ernst
  • Tim F Greten
  • Melek C Arkan
  • Thomas Korn
  • Dagmar Wirth
  • Florian R Greten

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…

Author Melek Canan Arkan

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…

Author Melek Canan Arkan

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

  • Manon D Schulz
  • Ciğdem Atay
  • Jessica Heringer
  • Franziska K Romrig
  • Sarah Schwitalla
  • Begüm Aydin
  • Paul K Ziegler
  • Julia Varga
  • Wolfgang Reindl
  • Claudia Pommerenke
  • Gabriela Salinas-Riester
  • Andreas Böck
  • Carl Alpert
  • Michael Blaut
  • Sara C Polson
  • Lydia Brandl
  • Thomas Kirchner
  • Florian R Greten
  • Shawn W Polson
  • Melek C Arkan

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…

  • Serkan I Göktuna
  • Ozge Canli
  • Julia Bollrath
  • Alexander A Fingerle
  • David Horst
  • Michaela A Diamanti
  • Charles Pallangyo
  • Moritz Bennecke
  • Tim Nebelsiek
  • Arun K Mankan
  • Roland Lang
  • David Artis
  • Yinling Hu
  • Thomas Patzelt
  • Jürgen Ruland
  • Thomas Kirchner
  • M Mark Taketo
  • Alain Chariot
  • Melek C Arkan
  • Florian R Greten

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…

  • Ning Li
  • Xuefeng Wu
  • Ryan G Holzer
  • Jun-Hee Lee
  • Jelena Todoric
  • Eek-Joong Park
  • Hisanobu Ogata
  • Anna S Gukovskaya
  • Ilya Gukovsky
  • Donald P Pizzo
  • Scott VandenBerg
  • David Tarin
  • Ciǧdem Atay
  • Melek C Arkan
  • Thomas J Deerinck
  • Jorge Moscat
  • Maria Diaz-Meco
  • David Dawson
  • Mert Erkan
  • Jörg Kleeff
  • Michael Karin

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…

  • Sarah Schwitalla
  • Alexander A Fingerle
  • Patrizia Cammareri
  • Tim Nebelsiek
  • Serkan I Göktuna
  • Paul K Ziegler
  • Ozge Canli
  • Jarom Heijmans
  • David J Huels
  • Guenievre Moreaux
  • Rudolf A Rupec
  • Markus Gerhard
  • Roland Schmid
  • Nick Barker
  • Hans Clevers
  • Roland Lang
  • Jens Neumann
  • Thomas Kirchner
  • Makoto M Taketo
  • Gijs R van den Brink
  • Owen J Sansom
  • Melek C Arkan
  • Florian R Greten

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…

  • Gitta M Seleznik
  • Theresia Reding
  • Franziska Romrig
  • Yasuyuki Saito
  • Alexander Mildner
  • Stephan Segerer
  • Li-Kang Sun
  • Stephan Regenass
  • Maciej Lech
  • Hans-Joachim Anders
  • Donal McHugh
  • Teru Kumagi
  • Yoichi Hiasa
  • Carolin Lackner
  • Johannes Haybaeck
  • Eliane Angst
  • Aurel Perren
  • Maria Luisa Balmer
  • Emma Slack
  • Andrew MacPherson
  • Markus G Manz
  • Achim Weber
  • Jeffrey L Browning
  • Melek Canan Arkan
  • Thomas Rülicke
  • Adriano Aguzzi
  • Marco Prinz
  • Rolf Graf
  • Mathias Heikenwalder

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…

  • Melanie Scheibel
  • Bettina Klein
  • Heidrun Merkle
  • Manon Schulz
  • Ralph Fritsch
  • Florian R Greten
  • Melek C Arkan
  • Günter Schneider
  • Roland M Schmid

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…

  • Melek C Arkan
  • Florian R Greten

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…

News

Canan Arkan appointed Professor for Tumor Metabolism

Canan Arkan appointed Professor for Tumor Metabolism at LOEWE-Centre FCI & Georg-Speyer-Haus

02.08.2023 Arkan

Jobs

Research Technician - Microbiome and Bacterial Cultivation

At the DKTK partner site Frankfurt/Mainz we are looking for a Technical Assistant (m/f/d) for the DKTK Joint Funding Project…

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…

Ph.D. Position in Microbiome-derived Factors on CAR-T Cell Therapy Research

This fully-funded Ph.D. position aims to explore how the human microbiome influences cancer biology and immunotherapy,…

Funding