PhD Scientific Days 2023

Molecular Sciences - Posters B

Identification of Regulators of Ferroptotic Cell Death in Melanoma

Előadó neve

Pál, Dorottya, MSc

Neptun code

PJDI3L

Előadó munkahelye

Semmelweis University, Department of Physiology

Előadó telefonszáma

+36707913570

Előadó e-mail címe

pal.dorottya@phd.semmelweis.hu

Az előadás címe

Identification of Regulators of Ferroptotic Cell Death in Melanoma

Szerző(k) neve és munkahelye

Dorottya Pál1, Alexandra Lakatos1, Anna Sára Lengyel, MD.2, Petra Péter 1, Botond Szabolcs 1, Elmar Lutz 1, Elisabeth M. Roider3, David E. Fisher MD,PhD.3 , Lajos V. Kemény MD, PhD.1,2,3

1 HCEMM-SU Translational Dermatology Research Group, Department of Physiology, Semmelweis University, Tűzoltó street 37-47. 1094 Budapest, Hungary
2 Department of Dermatology, Venerology and Dermatooncology, Semmelweis University, Mária street 41. 1085 Budapest, Hungary
3 Cutaneous Biology Research Center, Department of Dermatology and Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.

Bemutatás módja

Poszter

Szekció

Molecular Sciences - Posters B

Language of the presentation

Hungarian

Preferred session

Molecular Sciences

Összefoglaló szövege

Introduction: Given that lack of clinically available approaches to overcome resistance to modern targeted and immunotherapies for metastatic melanoma, a better understanding of cell death regulatory pathways is warranted in melanoma. Ferroptosis is a recently discovered lipid reactive oxygen radical-mediated, iron-dependent cell death that has shown particular promise in dedifferentiated, multi-drug resistant melanoma cell lines. However, it is unknown, why dedifferentiated melanoma cells are susceptible for ferroptotic cell death and why differentiated melanoma cells are resistant to ferroptosis.

Aims: We aim to investigate the regulation of ferroptotic cell death in melanoma.

Methods: We have performed siRNA mediated knockdown of MITF and assayed cellular ROS levels by DFCDA staining. We have utilized CTRPv2 database and correlated compound sensitivity with MITF levels across melanoma cell lines. We have performed in vitro viability assays in melanoma cell lines with or without siRNA mediated MITF downregulation and investigated the IC50 values of various ferroptotic compounds (ML210, RSL3) at 10 different concentrations.

Results: Our preliminary results show that MITF transcription factor protects differentiated melanoma cells from cell death caused by ROS. Bioinformatic analyses suggests that MITF mRNA levels inversely correlate with sensitivity to ferroptosis. However, our preliminary in vitro functional experiments suggest that MITF functionally does not consistently affect sensitivity to ferroptosis.

Conclusion: Thus, the regulation of ferroptosis in melanoma remains largely uncharacterized.. Therefore, new therapeutic targets promoting ferroptosis in differentiated and dedifferentiated melanoma cell lines are required. We plan to perform genome-wide in vitro crispr screen assays to identify melanoma specific regulators of ferroptosis. The expected outcome is the identification of several novel genes as therapeutic targets, 1, in preventing ferroptosis resistance in dedifferentiated melanoma and 2, sensitizing differentiated melanoma cells to ferroptosis cell death.

Funding: L.V.K. is a recipient of the János Bolyai Research Scholarship of the Hungarian Academy of Sciences and is supported by the Hungarian National Research, Development and Innovation Office (OTKA FK138696) grant, a STIA-KFI grant from Semmelweis University. The project has received funding from the EU’s Horizon 2020 research and innovation program under grant agreement no. 739593.

University and Doctoral School

Semmelweis University, Doctoral School of Molecular Medicine

Supervisor

Lajos Vince Kemény MD, PhD

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7351

Start

11:12

End

11:17

Authors (legacy)

Dorottya Pál1, Alexandra Lakatos1, Anna Sára Lengyel, MD.2, Petra Péter 1, Botond Szabolcs 1, Elmar Lutz 1, Elisabeth M. Roider3, David E. Fisher MD,PhD.3 , Lajos V. Kemény MD, PhD.1,2,3

1 HCEMM-SU Translational Dermatology Research Group, Department of Physiology, Semmelweis University, Tűzoltó street 37-47. 1094 Budapest, Hungary
2 Department of Dermatology, Venerology and Dermatooncology, Semmelweis University, Mária street 41. 1085 Budapest, Hungary
3 Cutaneous Biology Research Center, Department of Dermatology and Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.