PhD Scientific Days 2026

Pharmaceutical Sciences and Health Technologies 4.

Subtype-Specific Changes in Zinc Transport Associated with KRAS Mutations in Isogenic Cancer Cell Lines

Előadó neve

Dr. Üveges, Elina

Neptune code

GH8E3L

Előadó munkahelye

Semmelweis University, Doctoral School, Pharmaceutical Sciences and Health Technologies Division

Előadó telefonszáma

+36305626354

Előadó e-mail címe

uvegeselina@gmail.com

Az előadás címe

Subtype-Specific Changes in Zinc Transport Associated with KRAS Mutations in Isogenic Cancer Cell Lines

Szerző(k) neve és munkahelye

Elina Üveges¹, Norbert Szoboszlai², Marcell Baranyi³, Balázs Hegedűs⁴, Gergely Szakács⁵

1: Semmelweis University, Doctoral School, Pharmaceutical Sciences and Health Technologies Division
2: Integrative Health and Environmental Analysis Research Laboratory, Institute of Chemistry, ELTE Eötvös Loránd University, Budapest, Hungary
3: Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
4: Department of Thoracic Surgery, University Medicine Essen – Ruhrlandklinik, Essen, Germany
5: Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary

Bemutatás módja

Szóbeli

Szekció

Pharmaceutical Sciences and Health Technologies 4.

Language of the presentation

English

Preferred session

Pharmaceutical Sciences and Health Technologies

Összefoglaló szövege

Introduction:
Zinc is an essential trace element involved in cellular homeostasis, functioning as a cofactor for numerous enzymes and playing a key role in DNA replication. Emerging evidence highlights the importance of zinc regulation in cancer, particularly in breast and prostate tumors. KRAS is one of the most frequently mutated oncogenes across cancer types, with common variants including G12D, G12V, and G12C. Currently, targeted therapies are available only for the G12C subtype. Identifying metabolic differences between KRAS wild-type and mutant cells is therefore critical for developing selective treatments.
Aims:
This study aimed to investigate zinc uptake and accumulation across different KRAS subtypes using isogenic colorectal and lung cancer cell models, along with additional cancer cell lines harboring distinct KRAS mutations.
Methods:
Four-hour zinc uptake assays were performed in isogenic colorectal SW48 cell lines (wild-type, G12C, G12D, G12V) and lung adenocarcinoma H838 cell lines (wild-type, G12D, G12V), as well as other colorectal (HT-29, HCT116, SW480, SNUC2B) and lung (SW1573, H358, PF139, A427) cancer cell lines. Intracellular zinc levels were quantified using total reflection X-ray fluorescence (TXRF). The effect of the zinc chelator TPEN on cell growth and survival was assessed in SW48 KRAS mutants using the PrestoBlue™ viability assay.
Results:
KRAS G12D mutant cell lines exhibited significantly higher zinc accumulation compared to wild-type and other KRAS variants from the same tissue type following zinc sulfate treatment. Additionally, TPEN treatment (4 µM) caused a mild but consistent reduction in cell growth in SW48 G12D cells compared to wild-type, G12C, and G12V cells over 24–72 hours.
Conclusion:
KRAS G12D, G12C, and G12V mutants show significant differences in intracellular zinc accumulation. Although the underlying mechanisms remain unclear, identifying the responsible pathways and proteins may support the development of targeted therapies for KRAS G12D–driven cancers.

Funding
This work was funded by Semmelweis University Predoctoral Scholarship 2025/2026.

University

Semmelweis University

Supervisor

Dr. Szoboszlai Norbert

Publication of my abstract

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

phd.section.field

in doctoral studies after complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

jóváhagyta

Előadó

6883

Start

16:30

End

16:40