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Updated: Jan 1, 2026
In Vitro Evaluation of Oncogenic Transformation in Human Mammary Epithelial Cells
Published on: September 24, 2020
Genetic Programs Driving Oncogenic Transformation: Lessons from in Vitro Models
Eros Di Giorgio1, Harikrishnareddy Paluvai1, Raffaella Picco1
1Department of Medicine, Università degli Studi di Udine, P.le Kolbe 4, 33100 Udine, Italy.
Abstract:
Cancer complexity relies on the intracellular pleiotropy of oncogenes/tumor suppressors and in the strong interplay between tumors and micro- and macro-environments. Here we followed a reductionist approach, by analyzing the transcriptional adaptations induced by three oncogenes (RAS, MYC, and HDAC4) in an isogenic transformation process. Common pathways, in place of common genes became dysregulated. From our analysis it emerges that, during the process of transformation, tumor cells cultured in vitro prime some signaling pathways suitable for coping with the blood supply restriction, metabolic adaptations, infiltration of immune cells, and for acquiring the morphological plasticity needed during the metastatic phase. Finally, we identified two signatures of genes commonly regulated by the three oncogenes that successfully predict the outcome of patients affected by different cancer types. These results emphasize that, in spite of the heterogeneous mutational burden among different cancers and even within the same tumor, some common hubs do exist. Their location, at the intersection of the various signaling pathways, makes a therapeutic approach exploitable.
Insights
This study reveals common signaling pathway dysregulation during cancer development, driven by oncogenes like RAS, MYC, and HDAC4. These pathways help tumors adapt and predict patient outcomes, suggesting new therapeutic targets.
Area of Science:
- Molecular oncology and cancer biology.
- Transcriptional regulation and gene expression analysis in cancer.
Background:
- Cancer complexity arises from oncogene/tumor suppressor pleiotropy and tumor micro/macro-environment interactions.
- Understanding commonalities in cancer progression despite mutational heterogeneity is crucial.
Purpose of the Study:
- To analyze transcriptional adaptations induced by three key oncogenes (RAS, MYC, HDAC4) during isogenic transformation.
- To identify common dysregulated pathways and gene signatures predictive of cancer patient outcomes.
Main Methods:
- A reductionist approach analyzing transcriptional adaptations.
- Investigated the impact of RAS, MYC, and HDAC4 oncogenes in an isogenic transformation model.
- Identified common gene signatures regulated by these oncogenes.
Main Results:
- Common signaling pathways, rather than specific genes, were dysregulated during oncogene-induced transformation.
- Tumor cells in vitro prime pathways for adapting to environmental challenges like restricted blood supply and immune infiltration.
- Two gene signatures regulated by RAS, MYC, and HDAC4 predict patient outcomes across various cancer types.
Conclusions:
- Despite diverse mutational landscapes, common regulatory hubs exist at the intersection of signaling pathways in cancer.
- These common hubs offer potential therapeutic targets for a broad range of cancers.
- Transcriptional adaptations driven by oncogenes are key to tumor cell survival, metastasis, and therapeutic vulnerability.
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