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Cancer Cell Plasticity - Ketola Lab profiilikuva

Cancer Cell Plasticity - Ketola Lab

Tutkimusryhmä
01.09.2019 -
Lääketieteen laitos, Terveystieteiden tiedekunta
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The Cancer Cell Plasticity research group investigates how prostate cancer cells adopt stem-like, neuroplastic, and neuroendocrine states to drive therapy resistance and disease progression. The group studies how cancer cells transition between cellular states in response to both therapeutic pressure and signals from the tumor microenvironment. These include immune cell–derived factors, neural and neuroendocrine-associated programs, and mechanical cues such as extracellular matrix (ECM) stiffness, which actively regulate cancer cell behavior. The research integrates advanced imaging with functional genomics and epigenomics to capture dynamic changes in chromatin state and gene regulation. Genome-wide approaches (RNA-seq, ATAC-seq, ChIP-seq) are combined with live-cell high-content imaging, drug screening, and patient-derived models, including organoids and liquid biopsies. Zebrafish metastasis models are further used to study cancer cell dissemination and plasticity in vivo.

Key intrinsic regulators of plasticity have been identified, including transcription factors such as SIX2, which drive stem-like and androgen receptor–independent states through chromatin reprogramming. Key plasticity-associated effectors such as DPYSL5 supports neuroplasticity-associated phenotypes and antiandrogen resistance. In addition, DNA repair pathways, including the Fanconi anemia pathway (FANCI), support therapy resistance. Recent work demonstrates that ECM stiffness directly regulates chromatin accessibility and androgen receptor signaling, with stiff matrices promoting aggressive transcriptional programs associated with poor clinical outcome.

The overall goal is to identify novel therapeutic targets and biomarkers and to develop strategies to prevent or reverse treatment resistance in advanced prostate cancer.

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Muut ryhmän jäsenet

  • Tomas Darth
  • Pihla Isopahkala
  • Onni Niemi
  • Eero Haanpää
  • Aleksanteri Seppälä
  • Joosua Järvinen