Marie Arsenian Henriksson Group

Approaches to target the MYC oncoprotein to combat cancer

Neuroblastoma (NB), a tumor that arises from neural crest cells in the developing sympathetic nervous system, is the most common and deadly solid childhood tumor outside the CNS. NB cells show complex patterns of genetic defects, including specific chromosomal aberrations and MYCN amplification. This occurs in 40-50% of high-risk cases and is associated with advanced-stage disease, rapid tumor progression and a survival rate of less than 15%. An alternative treatment option for these children is therefore urgently needed.

Our research is focused on the MYCN oncogene in order to identify targets for development of novel anti-cancer therapies. To this end we will: 1) analyze the functional significance of MYCN-regulated microRNAs for NB pathogenesis; 2) characterize the role of MYCN in invasion and migration; 3) identify small compounds that selectively kill cells with high MYCN expression; 4) explore the normal function of MYCN during development of the nervous system.

It was recently shown that MYCN regulates expression of micro-RNAs in NB cells. We have demonstrated that miR-18a and miR- 19a from the oncogenic miR-17~92 cluster target and subsequently repress the expression of estrogen receptor ± (ESR1). Downregulation of mir-18a as well as ectopic ESR1 expression resulted in growth arrest and neuronal differentiation of NB cells. Importantly, we demonstrated expression of ESR1 in human fetal sympathetic ganglia suggesting a role during neuronal development. We propose that MYCN amplification may disrupt estrogen-signaling sensitivity in primitive sympathetic cells through downregulation of ESR1, thereby preventing normal neuroblast differentiation.

Collectively, our studies will give insights to the normal function of MYCN and its contribution to NB pathogenesis. This knowledge could serve as basis for development of novel cancer therapies for children with neuroblastoma as well as other diseases, since MYC is activated in many different malignancies.

Project Groups within the Marie Arsenian Henriksson Group

Christer Ericsson Project

Elena Kashuba Project

Vladimir Kashuba Project

Eva Klein Project

Publications 2014-2017

The MYCN Protein in Health and Disease.
Ruiz-Pérez M, Henley A, Arsenian-Henriksson M
Genes (Basel) 2017 Mar;8(4):

Proliferation and Survival of Embryonic Sympathetic Neuroblasts by MYCN and Activated ALK Signaling.
Kramer M, Ribeiro D, Arsenian-Henriksson M, Deller T, Rohrer H
J. Neurosci. 2016 Oct;36(40):10425-10439

MicroRNA-203 Inversely Correlates with Differentiation Grade, Targets c-MYC, and Functions as a Tumor Suppressor in cSCC.
Lohcharoenkal W, Harada M, Lovén J, Meisgen F, Landén N, Zhang L, et al
J. Invest. Dermatol. 2016 Dec;136(12):2485-2494

Regulation of Nuclear Hormone Receptors by MYCN-Driven miRNAs Impacts Neural Differentiation and Survival in Neuroblastoma Patients.
Ribeiro D, Klarqvist M, Westermark U, Oliynyk G, Dzieran J, Kock A, et al
Cell Rep 2016 Jul;16(4):979-93

Direct inhibition of c-Myc-Max heterodimers by celastrol and celastrol-inspired triterpenoids.
Wang H, Teriete P, Hu A, Raveendra-Panickar D, Pendelton K, Lazo J, et al
Oncotarget 2015 Oct;6(32):32380-95

COX/mPGES-1/PGE2 pathway depicts an inflammatory-dependent high-risk neuroblastoma subset.
Larsson K, Kock A, Idborg H, Arsenian Henriksson M, Martinsson T, Johnsen J, et al
Proc. Natl. Acad. Sci. U.S.A. 2015 Jun;112(26):8070-5

Acetylation of the c-MYC oncoprotein is required for cooperation with the HTLV-1 p30(II) accessory protein and the induction of oncogenic cellular transformation by p30(II)/c-MYC.
Romeo M, Ko B, Kim J, Brady R, Heatley H, He J, et al
Virology 2015 Feb;476():271-88

TAp73 suppresses tumor angiogenesis through repression of proangiogenic cytokines and HIF-1α activity.
Stantic M, Sakil H, Zirath H, Fang T, Sanz G, Fernandez-Woodbridge A, et al
Proc. Natl. Acad. Sci. U.S.A. 2015 Jan;112(1):220-5

Impact of MYC in regulation of tumor cell metabolism.
Wahlström T, Henriksson M
Biochim. Biophys. Acta 2015 May;1849(5):563-9

X-ray phase contrast with injected gas for tumor microangiography.
Lundström U, Westermark U, Larsson D, Burvall A, Arsenian Henriksson M, Hertz H
Phys Med Biol 2014 Jun;59(11):2801-11

MYC proteins promote neuronal differentiation by controlling the mode of progenitor cell division.
Zinin N, Adameyko I, Wilhelm M, Fritz N, Uhlén P, Ernfors P, et al
EMBO Rep. 2014 Apr;15(4):383-91

Book Chapters

Frenzel, A., and Arsenian Henriksson, M
MYC
Encyclopedia of Signalling Molecules, Springer Verlag. 2012
    •    Encyclopedia of Signalling Molecules

Publications 2006-2013

Publications 2010-2013 (pdf file)

publications 2006-2009 (pdf file)

Group Members

Professor

Marie Arsenian-Henriksson

Telefon: 08-524 862 05
Enhet: Marie Arsenian Henriksson grupp
E-post: Marie.Arsenian.Henriksson@ki.se

Samordnare

Barbro Ehlin-Henriksson

Telefon: 08-524 867 31
Enhet: Marie Arsenian Henriksson grupp
E-post: Barbro.Ehlin-Henriksson@ki.se

Postdoc

Johanna Dzieran

Enhet: Marie Arsenian Henriksson grupp
E-post: johanna.dzieran@ki.se

Postdoc

María Ruiz Pérez

Enhet: Marie Arsenian Henriksson grupp
E-post: maria.ruiz.perez@ki.se

Postdoc

AIDA RODRIGUEZ GARCIA

Enhet: Marie Arsenian Henriksson grupp
E-post: aida.rodriguez.garcia@ki.se

Associated

Áine Henley

E-post: aine.henley@ki.se

Anknuten

Elena Eyre Sánchez

Enhet: Marie Arsenian Henriksson grupp
E-post: elena.eyre.sanchez@ki.se

Forskarassistent

Catarina Träger

Enhet: Marie Arsenian Henriksson grupp
E-post: Catarina.Trager@ki.se

Professor, adj

Maria Bejarano

Enhet: Marie Arsenian Henriksson grupp
E-post: Maria.Bejarano@ki.se

Anknuten

Christer Ericsson

Telefon: 08-524 800 00
E-post: Christer.Ericsson@ki.se

Postdoc

Anders Mutvei

Enhet: Marie Arsenian Henriksson grupp
E-post: Anders.Mutvei@ki.se

Anknuten

Kerstin Falk

E-post: Kerstin.Falk@ki.se

Anknuten

Carmen Mihaela Vogt

Enhet: Marie Arsenian Henriksson grupp
E-post: carmen.vogt@ki.se

Professor emerita

Eva Klein

Telefon: 86774
Enhet: Marie Arsenian Henriksson grupp
E-post: Eva.Klein@ki.se

Anknuten

Noemi Nagy

Enhet: TIM
E-post: Noemi.Nagy@ki.se

Senior forskningsspecialist

Daniel Salamon

E-post: Daniel.Salamon@ki.se

Senior lab manager

Vladimir Kashuba

Enhet: Marie Arsenian Henriksson grupp
E-post: Vladimir.Kashuba@ki.se

Forskarstuderande

Twana Hasseb Abdulahad Alkasalias

Enhet: Marie Arsenian Henriksson grupp
E-post: twana.alkasalias@ki.se

Anknuten

Hayrettin Guven

Telefon: 08-524 867 61
E-post: Hayrettin.Guven@ki.se

Forskarstuderande

Benedek Bozoky

Enhet: Institutionen för mikrobiologi, tumör- och cellbiologi (MTC), C1
E-post: benedek.bozoky@ki.se

Anknuten

Vivian Ho

E-post: vivian.ho@ki.se

Anknuten

Nils Eickhoff

Telefon: 08-524 867 38
Enhet: Marie Arsenian Henriksson grupp
E-post: nils.eickhoff@ki.se

Visiting researcher

Ingibjorg Sigvaldadottir

E-post: ingibjorg.sigvaldadottir@stud.ki.se

Former Group Members

Former Group Members

Funding

We are indebted to the following organizations for their valuable support for our research! Thank you! 

Funds from the Karolinska Institutet