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ResearchIn-Press PreviewCell biologyOncology Free access | 10.1172/JCI143557
1The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
2Division of Hematology, Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America
3Breast Cancer Research Program, Vanderbilt University Medical Center, Nashville, United States of America
4Division of Hematology, Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America
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1The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
2Division of Hematology, Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America
3Breast Cancer Research Program, Vanderbilt University Medical Center, Nashville, United States of America
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1The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
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3Breast Cancer Research Program, Vanderbilt University Medical Center, Nashville, United States of America
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1The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
2Division of Hematology, Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America
3Breast Cancer Research Program, Vanderbilt University Medical Center, Nashville, United States of America
4Division of Hematology, Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America
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1The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
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3Breast Cancer Research Program, Vanderbilt University Medical Center, Nashville, United States of America
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3Breast Cancer Research Program, Vanderbilt University Medical Center, Nashville, United States of America
4Division of Hematology, Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America
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1The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States of America
2Division of Hematology, Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America
3Breast Cancer Research Program, Vanderbilt University Medical Center, Nashville, United States of America
4Division of Hematology, Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America
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Published February 2, 2021 - More info
Intratumor heterogeneity is an important mediator of poor outcomes in many cancers, including breast cancer. Genetic subclones frequently contribute to this heterogeneity, however their growth dynamics and interactions remain poorly understood. PIK3CA and HER2 alterations are known to co-exist in breast and other cancers. Herein, we present data that describe the ability of oncogenic PIK3CA mutant cells to induce the proliferation of quiescent HER2 mutant cells through a cell-contact mediated mechanism. Interestingly, the HER2 cells proliferated to become the major subclone over PIK3CA counterparts both in vitro and in vivo. Furthermore, this phenotype was observed in both hormone receptor positive and negative cell lines, and was dependent on the expression of fibronectin from mutant PIK3CA cells. Analysis of human tumors demonstrated similar HER2:PIK3CA clonal dynamics and fibronectin expression. Our study provides insights into non-random subclonal architecture of heterogenous tumors, which may aid understanding of tumor evolution and future strategies for personalized medicine.