ArticleCancer discovery2023
Dynamic Glycoprotein Hyposialylation Promotes Chemotherapy Evasion and Metastatic Seeding of Quiescent Circulating Tumor Cell Clusters in Breast Cancer.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 53 citations in OpenAlex.
- Aberrant sialylation in cancer: From molecular mechanisms to potential therapeutics.Genes & diseases · 2026Review
- The immune phenotype of circulating tumor cells: from escape mechanisms to immunotherapy navigation.Biomarker research · 2026Review
- Article
- CD97/Cells · 2026Review
- The sleeping threat: targeting cancer dormancy to transform metastasis therapy.Nature reviews. Cancer · 2026Review
- CAFs-derived LAM332 promotes CTCs formation and survival via ITGA3 and contributes to the metastasis of pancreatic ductal adenocarcinoma.Cell death & disease · 2026Article
- Targeting sialic acid metabolism: a therapeutic strategy against gastric cancer driven by WZ35.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Integrating plasma protein-centric multi-omics to evaluate the causal effect of glycosylation on the risk of cancer.Glycoconjugate journal · 2026Article
- Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis.Signal transduction and targeted therapy · 2026Review
- Targeting the tripartite axis of immune-metabolic-spatial crosstalk to overcome therapy resistance in breast cancer.Frontiers in immunology · 2026Review
- P-glycoprotein 1 as a shared target for resensitizing drug-resistant tumor cells and preventing fibronectin-driven metastasis.Theranostics · 2026Article
- Sialylation in Thyroid Carcinoma: An Overview of Mechanisms, Markers, and Therapeutic Opportunities.Journal of Cancer · 2026Review
- Machine Learning-Based Sialylation-Associated Gene Signature Predicts Prognosis and Immune Landscape in Hepatocellular Carcinoma: Validation via Multi-Omics Analysis and in vitro Assays.Journal of hepatocellular carcinoma · 2026Article
- Machine learning-driven comprehensive profiling of tumor heterogeneity and sialylation in hepatocellular carcinoma.NPJ precision oncology · 2025Article
- Unfolded protein response kinase PERK supports survival and metastasis of circulating tumor cell clusters via SAM synthesis and H3K4me3-dependent PDGFB signaling.Cancer communications (London, England) · 2025Article
- Double-positive T cells form heterotypic clusters with circulating tumor cells to foster cancer metastasis.The Journal of clinical investigation · 2025Article
- Clinical applications of circulating tumor cells in metastasis and therapy.Journal of hematology & oncology · 2025Review
- c-MET Inhibition Reverses the Osimertinib Resistance in Lung Circulating Tumor Cell Clusters and Suppresses Metastasis.Biological procedures online · 2025Article
- Computational ranking identifies Plexin-B2 in circulating tumor cell clustering with monocytes in breast cancer metastasis.Nature communications · 2025Article
- A Cancer-Specific Anti-Podocalyxin Monoclonal Antibody (humPcMab-60) Demonstrated Antitumor Efficacy in Pancreatic and Colorectal Cancer Xenograft Models.Antibodies (Basel, Switzerland) · 2025Article
Corrections and comments
- Commented on by
Authors and funding
29 authors at 4 institutions in 2 countries.
Funding
Abstract
Most circulating tumor cells (CTC) are detected as single cells, whereas a small proportion of CTCs in multicellular clusters with stemness properties possess 20- to 100-times higher metastatic propensity than the single cells. Here we report that CTC dynamics in both singles and clusters in response to therapies predict overall survival for breast cancer. Chemotherapy-evasive CTC clusters are relatively quiescent with a specific loss of ST6GAL1-catalyzed α2,6-sialylation in glycoproteins. Dynamic hyposialylation in CTCs or deficiency of ST6GAL1 promotes cluster formation for metastatic seeding and enables cellular quiescence to evade paclitaxel treatment in breast cancer. Glycoproteomic analysis reveals newly identified protein substrates of ST6GAL1, such as adhesion or stemness markers PODXL, ICAM1, ECE1, ALCAM1, CD97, and CD44, contributing to CTC clustering (aggregation) and metastatic seeding. As a proof of concept, neutralizing antibodies against one newly identified contributor, PODXL, inhibit CTC cluster formation and lung metastasis associated with paclitaxel treatment for triple-negative breast cancer. SIGNIFICANCE: This study discovers that dynamic loss of terminal sialylation in glycoproteins of CTC clusters contributes to the fate of cellular dormancy, advantageous evasion to chemotherapy, and enhanced metastatic seeding. It identifies PODXL as a glycoprotein substrate of ST6GAL1 and a candidate target to counter chemoevasion-associated metastasis of quiescent tumor cells. This article is featured in Selected Articles from This Issue, p. 1949.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.