2.2. 2023, Mitochondriální fyziologie

Laboratory name: Mitochondrial physiology

Laboratory website

PhD project: Targeting tamoxifen resistance in breast carcinoma: the role of glycerophospholipid metabolism

Breast carcinoma is the most common oncological disorder among women. Hormone therapy targeted to estrogen receptor (ER) positive cases often fails due to the primary and secondary resistance, which leads to cancer progression and mortality. There is an urgent need for molecular markers, which reflect the actual activity of the ER pathway, or another indicator of the resistance. We presume that molecular markers and potential therapeutic targets might be components of cancer metabolic phenotype developed during tamoxifen treatment.

 In this project, we plan to use a novel cell model of secondary resistance to tamoxifen (Tam5R) developed in the laboratory of our collaborator. We will focus on functional analysis of glycerophospholipid pathways with emphasis on phosphatidylinositol and cardiolipin metabolism, which we have found significantly upregulated in Tam5R cells. Moreover, growth of Tam5R cells was selectively affected by deletion of genes in the named pathways.  We will further use cell-derived xenografts to assess functional impact of the named metabolic pathways in vivo. The overall goal of the project is to reveal molecular mechanisms, by which metabolic remodeling affects sensitivity to tamoxifen and promotes cancer growth under hormone therapy treatment. The project will be conducted in collaboration with IBT CAS.

References:

Tomková V, Sandoval-Acuña C, Torrealba N, Truksa J. Mitochondrial fragmentation, elevated mitochondrial superoxide and respiratory supercomplexes disassembly is connected with the tamoxifen-resistant phenotype of breast cancer cells. Free Radic Biol Med. 2019
Špačková J, Gotvaldová K, Dvořák A, Urbančoková A, Pospíšilová K, Větvička D, Leguina-Ruzzi A, Tesařová P, Vítek L, Ježek P, Smolková K. Biochemical Background in Mitochondria Affects 2HG Production by IDH2 and ADHFE1 in Breast Carcinoma. Cancers. 2021

Supervisor (email): Katarína Smolková, katarina.smolkova@fgu.cas.cz

Candidate’s profile (requirements): We are seeking outstanding self-motivated candidates with master's degree or equivalent in molecular biology, biochemistry, physiology, medicine or related fields, or those expecting to obtain their degree this year. Candidates should be fluent in English. Experience with in vitro cell cultures,  molecular biology techniques, and programming skills are advantage.