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Updated: Jul 23, 2025
Micromanipulation of Circulating Tumor Cells for Downstream Molecular Analysis and Metastatic Potential Assessment
Published on: May 14, 2019
Metastasis Unleashed: Hyposialylation Empowers Chemo-Evasive Circulating Tumor Cell Clusters in Breast Cancer
Ana Gvozdenovic1, Nicola Aceto1
1Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich, Switzerland.
Abstract:
Therapy resistance is frequently observed in cancer patients with distant metastases and effective management of metastatic disease remains challenging. Unraveling the cellular mechanisms and molecular targets fueling metastatic spread is crucial for advancing cancer therapies. In a recent issue of Cancer Discovery, Dashzeveg and colleagues revealed that loss of terminal sialylation in glycoproteins within circulating tumor cell clusters is a dynamic process that contributes to cellular dormancy, facilitates evasion of chemotherapy, and enhances metastatic seeding. Furthermore, the study identifies the glycoprotein podocalyxin (PODXL) as a potential target for counteracting the metastasis of quiescent tumor cells associated with paclitaxel treatment in triple-negative breast cancer.
Insights
Cancer cells evade chemotherapy by losing sialylation, promoting dormancy and metastasis. Researchers identified podocalyxin (PODXL) as a target to block this process in triple-negative breast cancer.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Medicine
Background:
- Therapy resistance and distant metastases pose significant challenges in cancer management.
- Understanding the mechanisms of metastatic spread is critical for developing effective cancer treatments.
Purpose of the Study:
- To investigate the role of cellular mechanisms and molecular targets in promoting cancer metastasis.
- To identify strategies to overcome therapy resistance in metastatic cancer.
Main Methods:
- Analysis of circulating tumor cell clusters.
- Assessment of glycoprotein terminal sialylation.
- Investigation of cellular dormancy and chemotherapy evasion.
- Evaluation of podocalyxin (PODXL) as a therapeutic target.
Main Results:
- Loss of terminal sialylation in glycoproteins within circulating tumor cell clusters was identified as a key process.
- This sialylation loss promotes cellular dormancy, chemotherapy evasion, and enhances metastatic seeding.
- Podocalyxin (PODXL) was identified as a potential therapeutic target.
Conclusions:
- Dynamic changes in sialylation, particularly loss of terminal sialylation, are crucial for metastatic progression and therapy evasion.
- Targeting PODXL may offer a strategy to inhibit metastasis in quiescent tumor cells, especially in the context of paclitaxel treatment for triple-negative breast cancer.
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