ArticleCancer discovery2019
Homophilic CD44 Interactions Mediate Tumor Cell Aggregation and Polyclonal Metastasis in Patient-Derived Breast Cancer Models.
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Article in Cancer discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers, 1 of them a synthesis that pooled it.
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237citing papers in PubMed, 1 pooled it
14.2field-weighted citation impact, top 1% of its field
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Who cites it
237 citing papers in PubMed, 1 synthesis or guideline pooled it, 402 citations in OpenAlex.
- Correlation between PD-L1 expression ON CTCs and prognosis of patients with cancer: a systematic review and meta-analysis.Oncoimmunology · 2021Pooled it
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- Micro/Nanostructured Materials and Microfluidic Diagnostic Platforms Enable Multimodal Detection of Circulating Tumor Cells.Exploration (Beijing, China) · 2026Review
- USF2-Mediated APOE-Cholesterol Signaling Promotes CTC Clustering and Metastasis in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2026Article
- Epithelial-mesenchymal transition in carcinoma: navigating phenotypic states to target resistance and metastasis.Cancer metastasis reviews · 2026Review
- An immunocompetent osteoblastic model of mammary cancer bone metastasis established by syngeneic intratibial injection of PyMT mammary carcinoma cells in FVB/N mice.bioRxiv : the preprint server for biology · 2026Article
- Identification of epithelial, mesenchymal, and platelet-associated circulating tumour cells with translational implications in oral squamous cell carcinoma.Scientific reports · 2026Article
- Tumor-enriched circRNA TAFCR1 drives cancer progression and metastasis by disrupting UBE1-dependent TRIM21-mediated CD44 ubiquitination.Biomarker research · 2026Article
- Multimodal machine learning integrates clinical and comorbidity data to predict breast cancer prognosis and treatment outcomes.Scientific reports · 2026Article
- Key molecular mechanisms and regulatory networks in colorectal cancer liver metastasis.Biological procedures online · 2026Review
- Circulating Tumor Cells: Emerging Frontiers in Cancer Technology.Expert reviews in molecular medicine · 2026Review
- Do Metastatic Cells Arise from PD-L1International journal of molecular sciences · 2026Review
- Extracellular matrix mediates circulating tumor cell clustering in triple-negative breast cancer metastasis.Nature communications · 2026Article
- PRDM16 Regulates Prostate Cancer Cell Dormancy and Prevents Bone Metastatic Outgrowth.Cancer research · 2026Article
- Fast label-free live imaging with FlowVision reveals key principles of cancer cell arrest on endothelial monolayers.The EMBO journal · 2026Article
- Liquid biopsies for detection, characterization, and interception of therapy resistance in thoracic malignancies.Frontiers in oncology · 2026Review
- Multi-omics analysis unveils tumor heterogeneity and immunotherapy predictive model in breast cancer for precision medicine and early detection.Neoplasia (New York, N.Y.) · 2026Article
- Role of circulating tumor cell clusters in breast cancer.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026Review
- Scaffold-free 3D-cell co-culture model system for the study of metastatic cancer in the brain TME.PloS one · 2026Article
- Breast cancer stem cells and circulating tumor cells: Dual drivers of progression and relapse.World journal of stem cells · 2025Review
177 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 6 institutions in 2 countries.
Xia LiuDepartment of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. huiping.liu@northwestern.edu john.condeelis@einstein.yu.edu xia.liu@northwestern.edu.
Rokana TaftafDepartment of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Madoka KawaguchiDepartment of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Ya-Fang ChangThe Ben May Department for Cancer Research, The University of Chicago, Chicago, Illinois.
Wenjing ChenDepartment of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
David EntenbergDeparment of Anatomy and Structural Biology, Gruss Lipper Biophotonics Center, Integrated Imaging Program, Albert Einstein College of Medicine, Bronx, New York.ORCID 0000-0003-0422-7264
Youbin ZhangDepartment of Medicine, Hematology/Oncology Division, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Lorenzo GerratanaDepartment of Medicine, Hematology/Oncology Division, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.ORCID 0000-0002-8313-4834
Simo HuangDeparment of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
Dhwani B PatelDepartment of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Elizabeth TsuiDepartment of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Valery Adorno-CruzDepartment of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Steven M ChirieleisonDeparment of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio.ORCID 0000-0002-3997-5652
Yue CaoDepartment of Electrical and Computer Engineering, TEES-AgriLife Center for Bioinformatics and Genomic Systems Engineering, Texas A&M University, College Station, Texas.
Allison S HarneyDeparment of Anatomy and Structural Biology, Gruss Lipper Biophotonics Center, Integrated Imaging Program, Albert Einstein College of Medicine, Bronx, New York.
Shivani PatelDeparment of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
Antonia PatsialouDeparment of Anatomy and Structural Biology, Gruss Lipper Biophotonics Center, Integrated Imaging Program, Albert Einstein College of Medicine, Bronx, New York.
Yang ShenDepartment of Electrical and Computer Engineering, TEES-AgriLife Center for Bioinformatics and Genomic Systems Engineering, Texas A&M University, College Station, Texas.ORCID 0000-0002-1703-7796
Stefanie AvrilDeparment of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
Hannah L GilmoreDeparment of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
Justin D LathiaDepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio.
Derek W AbbottDeparment of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio.ORCID 0000-0003-4387-8094
Massimo CristofanilliDepartment of Medicine, Hematology/Oncology Division, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
John S CondeelisDeparment of Anatomy and Structural Biology, Gruss Lipper Biophotonics Center, Integrated Imaging Program, Albert Einstein College of Medicine, Bronx, New York. huiping.liu@northwestern.edu john.condeelis@einstein.yu.edu xia.liu@northwestern.edu.ORCID 0000-0001-8826-2336
Huiping LiuDepartment of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. huiping.liu@northwestern.edu john.condeelis@einstein.yu.edu xia.liu@northwestern.edu.
Northwestern University · USCase Western Reserve University · USAlbert Einstein College of Medicine · USTexas A&M University System · USCleveland Clinic Lerner College of Medicine · USMay Institute · US
Funding
TUMOR METABOLISM PROGRAMP30CA043703 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI MARK R CHANCE · 1987 to 2026
$142.3MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4MTumor Progression and MetastasisP01CA100324 · NCI · YESHIVA UNIVERSITY · PI CONDEELIS, JOHN S · 2003 to 2018
$30.0MInstitutional Career Development CoreKL2TR002547 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI DWEIK, RAED A. · 2018 to 2022
$7.7MTRAINING PROGRAM IN ONCOGENESIS &DEVELOPMENT BIOLOGYT32CA080621 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI EKLUND, ELIZABETH ANN · 2001 to 2018
$4.1MInnate Immune Signal Transduction Specificity in Inflammatory DiseaseR01GM086550 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI ABBOTT, DEREK W · 2009 to 2020
$3.8MSignal transduction regulating tumor cell disseminationR01CA150344 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CONDEELIS, JOHN S · 2010 to 2020
$3.7MImmunology Training Program-PredoctoralT32AI089474 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI COBB, BRIAN A · 2010 to 2025
$3.4M(7) Novel imaging devices for measurement and control of tumor microenvironmentsR01CA216248 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CADY, NATHANIEL CHARLES, CONDEELIS, JOHN S · 2017 to 2021
$2.9MUnraveling molecular and system-level mechanisms of human disease-associated protein mutationsR35GM124952 · NIGMS · TEXAS ENGINEERING EXPERIMENT STATION · PI Yang Shen · 2017 to 2026
$2.9MMICROENVIRONMENTS OF INVASION IN HUMAN BREAST TUMORSR01CA113395 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI CONDEELIS, JOHN S · 2006 to 2010
$1.4MIdentifying a network of miRNAs and genes that regulate breast tumor metastasisR00CA160638 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LIU, HUIPING · 2014 to 2017
$883kNCATS NIH HHS KL2 TR002547NCI NIH HHS K99 CA160638NCI NIH HHS P01 CA100324NCI NIH HHS P30 CA043703NCI NIH HHS R00 CA160638NCI NIH HHS R01 CA113395NCI NIH HHS R01 CA150344NCI NIH HHS R01 CA216248NCI NIH HHS T32 CA080621NIAID NIH HHS T32 AI089474NIGMS NIH HHS R01 GM086550NIGMS NIH HHS R35 GM124952NIGMS NIH HHS T32 GM007250
Abstract
Circulating tumor cells (CTC) seed cancer metastases; however, the underlying cellular and molecular mechanisms remain unclear. CTC clusters were less frequently detected but more metastatic than single CTCs of patients with triple-negative breast cancer and representative patient-derived xenograft models. Using intravital multiphoton microscopic imaging, we found that clustered tumor cells in migration and circulation resulted from aggregation of individual tumor cells rather than collective migration and cohesive shedding. Aggregated tumor cells exhibited enriched expression of the breast cancer stem cell marker CD44 and promoted tumorigenesis and polyclonal metastasis. Depletion of CD44 effectively prevented tumor cell aggregation and decreased PAK2 levels. The intercellular CD44-CD44 homophilic interactions directed multicellular aggregation, requiring its N-terminal domain, and initiated CD44-PAK2 interactions for further activation of FAK signaling. Our studies highlight that CD44
Indexed as
Neoplasm MetastasisAnimalsBiomarkers, TumorCarcinogenesisFemaleHumansHyaluronan ReceptorsMiceNeoplastic Cells, Circulatingp21-Activated KinasesTriple Negative Breast NeoplasmsXenograft Model Antitumor AssaysBiomarkers, TumorCD44 protein, humanHyaluronan Receptorsp21-Activated Kinases
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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.