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

Neuroblast differentiation during development and in neuroblastoma requires KIF1Bβ-mediated transport of TRKA.
Fell S, Li S, Wallis K, Kock A, Surova O, Rraklli V, et al
Genes Dev. 2017 May;31(10):1036-1053

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

Phone: +46-(0)8-524 862 05
Organizational unit: Marie Arsenian Henriksson group
E-mail: Marie.Arsenian.Henriksson@ki.se

Professor emerita

Eva Klein

Phone: 86774
Organizational unit: Marie Arsenian Henriksson group
E-mail: Eva.Klein@ki.se

Coordinator

Barbro Ehlin-Henriksson

Phone: +46-(0)8-524 867 31
Organizational unit: Marie Arsenian Henriksson group
E-mail: Barbro.Ehlin-Henriksson@ki.se

Postdoc

Johanna Dzieran

Organizational unit: Marie Arsenian Henriksson group
E-mail: johanna.dzieran@ki.se

PhD student

Ganna Oliynyk

Organizational unit: Marie Arsenian Henriksson group
E-mail: ganna.oliynyk@ki.se

Postdoc

María Ruiz Pérez

Organizational unit: Marie Arsenian Henriksson group
E-mail: maria.ruiz.perez@ki.se

Postdoc

AIDA RODRIGUEZ GARCIA

Organizational unit: Marie Arsenian Henriksson group
E-mail: aida.rodriguez.garcia@ki.se

Associated

Áine Henley

E-mail: aine.henley@ki.se

Associated

Elena Eyre Sánchez

Organizational unit: Marie Arsenian Henriksson group
E-mail: elena.eyre.sanchez@ki.se

Assistant professor

Catarina Träger

Organizational unit: Marie Arsenian Henriksson group
E-mail: Catarina.Trager@ki.se

Associated

Nils Eickhoff

Phone: +46-(0)8-524 867 38
Organizational unit: Marie Arsenian Henriksson group
E-mail: nils.eickhoff@ki.se

Adjunct professor

Maria Bejarano

Organizational unit: Marie Arsenian Henriksson group
E-mail: Maria.Bejarano@ki.se

Associated

Vivian Ho

E-mail: vivian.ho@ki.se

Associated

Christer Ericsson

Phone: +46-(0)8-524 800 00
E-mail: Christer.Ericsson@ki.se

Postdoc

Anders Mutvei

Organizational unit: Marie Arsenian Henriksson group
E-mail: Anders.Mutvei@ki.se

Associated

Kerstin Falk

E-mail: Kerstin.Falk@ki.se

Associated

Carmen Mihaela Vogt

Organizational unit: Marie Arsenian Henriksson group
E-mail: carmen.vogt@ki.se

Senior research specialist

Daniel Salamon

E-mail: Daniel.Salamon@ki.se

Senior lab manager

Vladimir Kashuba

Organizational unit: Marie Arsenian Henriksson group
E-mail: Vladimir.Kashuba@ki.se

Graduate Student

Twana Hasseb Abdulahad Alkasalias

Organizational unit: Marie Arsenian Henriksson group
E-mail: twana.alkasalias@ki.se

Associated

Hayrettin Guven

Phone: +46-(0)8-524 867 61
E-mail: Hayrettin.Guven@ki.se

Graduate Student

Benedek Bozoky

Organizational unit: Ingemar Ernberg group
E-mail: benedek.bozoky@ki.se

Senior researcher

Elena Kashuba

Phone: +46-(0)8-524 862 59
Organizational unit: Marie Arsenian Henriksson group
E-mail: Elena.Kashuba@ki.se

Research assistant

Muhammad Mushtaq

E-mail: muhammad.mushtaq@ki.se

Student

Mark Fábián

Student

Dan-Mircea Mirea

Student

Karolina Höse

Student

Hanna Tamas

 

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