ArticleHepatology (Baltimore, Md.)2018
Stochastic phenotype switching leads to intratumor heterogeneity in human liver cancer.
Article in Hepatology (Baltimore, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 22 citations in OpenAlex.
- MRI findings of intrahepatic cholangiocarcinoma with sarcomatoid differentiation: a retrospective case series.BMC medical imaging · 2026Article
- Developing an interpretable machine learning model via SHAP to predict HCC postoperative survival based on tumor immune microenvironment CODEX immunomics and MRI.Cancer imaging : the official publication of the International Cancer Imaging Society · 2026Article
- Enhancing breast cancer diagnosis: non-invasive prediction of MKI-67 (Ki67) expression using ultrasound images.BMC cancer · 2025Article
- Using deep learning to decipher the impact of telomerase promoter mutations on the dynamic metastatic morpholome.PLoS computational biology · 2024Article
- The epithelial-mesenchymal plasticity landscape: principles of design and mechanisms of regulation.Nature reviews. Genetics · 2023Review
- Epidemiological and Clinical Characteristics of Five Rare Pathological Subtypes of Hepatocellular Carcinoma.Frontiers in oncology · 2022Article
- Epigenetic instability may alter cell state transitions and anticancer drug resistance.PLoS computational biology · 2021Article
- Primary Liver Sarcomatoid Carcinoma: A Case Series and Literature Review.Journal of hepatocellular carcinoma · 2021Article
- Intratumoral heterogeneity of hepatocellular carcinoma: From single-cell to population-based studies.World journal of gastroenterology · 2020Review
- Establishment and Characterization of Two Novel Cholangiocarcinoma Cell Lines.Annals of surgical oncology · 2019Article
- MicroRNA Control of TGF-β Signaling.International journal of molecular sciences · 2018Review
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8 authors at 3 institutions in 3 countries.
Funding
Abstract
Intratumor heterogeneity is increasingly recognized as a major factor impacting diagnosis and personalized treatment of cancer. We characterized stochastic phenotype switching as a mechanism contributing to intratumor heterogeneity and malignant potential of liver cancer. Clonal analysis of primary tumor cell cultures of a human sarcomatoid cholangiocarcinoma identified different types of self-propagating subclones characterized by stable (keratin-7-positive or keratin-7-negative) phenotypes and an unstable phenotype consisting of mixtures of keratin-7-positive and keratin-7-negative cells, which lack stem cell features but may reversibly switch their phenotypes. Transcriptome sequencing and immunohistochemical studies with the markers Zeb1 and CD146/MCAM demonstrated that switching between phenotypes is linked to changes in gene expression related but not identical to epithelial-mesenchymal transition. Stochastic phenotype switching occurred during mitosis and did not correlate with changes in DNA methylation. Xenotransplantation assays with different cellular subclones demonstrated increased tumorigenicity of cells showing phenotype switching, resulting in tumors morphologically resembling the invasive component of primary tumor and metastasis.
conclusionOur data demonstrate that stochastic phenotype switching contributes to intratumor heterogeneity and that cells with a switching phenotype have increased malignant potential. (Hepatology 2017).
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