Biology subjects

Balacescu, L.

Publications and source records attributed to Balacescu, L..

2 recordsLinked to original sources

bioRxiv2026

Whole transcriptome analysis reveals ELK3 as a key driver of metastasis through regulation of 3D migration and stemness in triple-negative breast cancer cells

Metastasis is the leading cause of mortality in breast cancer and remains largely untargeted therapeutically. Identifying molecular drivers of metastatic progression is essential for developing effective treatments. This study investigated the role of the transcription factor ELK3 in triple-negative breast cancer (TNBC) metastasis by defining the cellular and molecular processes it regulates. MDA231 cells with ELK3 overexpression (OE) or knockdown (KD) were generated by lentiviral transduction. Transcriptomic alterations induced by ELK3-KD were analyzed by microarray and validated by RT-qPCR. Ingenuity Pathway Analysis and Gene Set Enrichment Analysis identified ELK3-dependent metastasis-associated pathways, which were functionally validated using 3D microfluidic migration assays, mammosphere formation assays, and flow cytometry/ AlamarBlue proliferation assays. High ELK3 expression correlated with a mesenchymal phenotype in BC cell lines and lymph node invasion in patient tumors. ELK3-KD significantly altered 740 genes, many linked to migration and stemness. Functionally, ELK3 enhanced 3D confined migration, likely through regulation of EMT, cell adhesion and protrusion formation. ELK3 also promoted cancer stem cell traits, potentially via hypoxia-related and WNT/{beta}-catenin, JAK/STAT3, TGF-{beta}, Notch1, and NF-{kappa}B signaling pathways. Additionally, ELK3 induced cellular quiescence while suppressing proliferation under adherent conditions. Overall, ELK3 acts as a pro-metastatic regulator in TNBC by promoting migration and stemness.

cancer biology↗

bioRxiv2025

Exploring Mechanisms of Early Acquired Resistance to Doxorubicin in Melanoma in 3D Model

This study investigated the mechanisms underlying early settlement of doxorubicin (DOX) resistance in B16.F10 murine melanoma spheroids, following repeated exposure to a subinhibitory concentration of the drug. Melanoma spheroids were twice treated with DOX for 48h with a 48h recovery period, and changes in viability, growth, gene/protein expression, and enzyme activity were assessed using RNA-seq, RT-qPCR, western blot, protein array, and gelatinase assays. DOX exposure triggered a biphasic response in melanoma spheroids, with the initial exposure downregulating transcripts involved in cell cycle, DNA damage and repair responses, and suppressing of TNF- via NF-{kappa}B and mTORC1 stress response-related signaling pathways, indicating cell cycle arrest, enhanced DNA damage, and apoptosis resistance. Concurrently, upregulation of Notch1, and of angiogenic, adhesion, and ECM remodeling genes and proteins indicated early DOX-adaptive responses aimed at evading checkpoint arrest and increasing cell aggressiveness. A second DOX exposure amplified these responses in melanoma spheroids, leading to upregulation of some genes involved in cell cycle progression, DNA repair damage responses, along with increased Aqp1, VEGF, Ackr3, MMP-2 expression, as well as elevated MMP-9 activity. Our results offer valuable insights into the molecular drivers of chemoresistance, revealing that early DOX-resistance in melanoma arises from adaptive mechanisms that support cell survival through enhanced angiogenesis and cell migration and motility capacity.

cancer biology↗