A functional genomic screen in vivo identifies CEACAM5 as a clinically relevant driver of breast cancer metastasis

Emily Powell, Jiansu Shao, Hector M. Picon, Christopher Bristow, Zhongqi Ge, Michael Peoples, Frederick Robinson, Sabrina L. Jeter-Jones, Christopher Schlosberg, Caitlin L. Grzeskowiak, Fei Yang, Yun Wu, Ignacio Wistuba, Stacy L. Moulder, William F. Symmans, Kenneth L. Scott, John R. Edwards, Han Liang, Timothy P. Heffernan, Helen Piwnica-Worms

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Tumor cells disseminate early in tumor development making metastasis-prevention strategies difficult. Identifying proteins that promote the outgrowth of disseminated tumor cells may provide opportunities for novel therapeutic strategies. Despite multiple studies demonstrating that the mesenchymal-to-epithelial transition (MET) is critical for metastatic colonization, key regulators that initiate this transition remain unknown. We serially passaged lung metastases from a primary triple negative breast cancer xenograft to the mammary fat pads of recipient mice to enrich for gene expression changes that drive metastasis. An unbiased transcriptomic signature of potential metastatic drivers was generated, and a high throughput gain-of-function screen was performed in vivo to validate candidates. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) was identified as a metastatic driver. CEACAM5 overproduction enriched for an epithelial gene expression pattern and facilitated tumor outgrowth at metastatic sites. Tissues from patients with metastatic breast cancer confirmed elevated levels of CEACAM5 in lung metastases relative to breast tumors, and an inverse correlation between CEACAM5 and the mesenchymal marker vimentin was demonstrated. Thus, CEACAM5 facilitates tumor outgrowth at metastatic sites by promoting MET, warranting its investigation as a therapeutic target and biomarker of aggressiveness in breast cancer.

Original languageEnglish (US)
Article number9
Journalnpj Breast Cancer
Volume4
Issue number1
DOIs
StatePublished - Dec 1 2018

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Carcinoembryonic Antigen
Cell Adhesion Molecules
Breast Neoplasms
Neoplasm Metastasis
Epithelial-Mesenchymal Transition
Neoplasms
Triple Negative Breast Neoplasms
Gene Expression
Lung
Vimentin
Heterografts
Adipose Tissue
Breast
Biomarkers
Therapeutics
Proteins

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)

Cite this

A functional genomic screen in vivo identifies CEACAM5 as a clinically relevant driver of breast cancer metastasis. / Powell, Emily; Shao, Jiansu; Picon, Hector M.; Bristow, Christopher; Ge, Zhongqi; Peoples, Michael; Robinson, Frederick; Jeter-Jones, Sabrina L.; Schlosberg, Christopher; Grzeskowiak, Caitlin L.; Yang, Fei; Wu, Yun; Wistuba, Ignacio; Moulder, Stacy L.; Symmans, William F.; Scott, Kenneth L.; Edwards, John R.; Liang, Han; Heffernan, Timothy P.; Piwnica-Worms, Helen.

In: npj Breast Cancer, Vol. 4, No. 1, 9, 01.12.2018.

Research output: Contribution to journalArticle

Powell, E, Shao, J, Picon, HM, Bristow, C, Ge, Z, Peoples, M, Robinson, F, Jeter-Jones, SL, Schlosberg, C, Grzeskowiak, CL, Yang, F, Wu, Y, Wistuba, I, Moulder, SL, Symmans, WF, Scott, KL, Edwards, JR, Liang, H, Heffernan, TP & Piwnica-Worms, H 2018, 'A functional genomic screen in vivo identifies CEACAM5 as a clinically relevant driver of breast cancer metastasis', npj Breast Cancer, vol. 4, no. 1, 9. https://doi.org/10.1038/s41523-018-0062-x
Powell, Emily ; Shao, Jiansu ; Picon, Hector M. ; Bristow, Christopher ; Ge, Zhongqi ; Peoples, Michael ; Robinson, Frederick ; Jeter-Jones, Sabrina L. ; Schlosberg, Christopher ; Grzeskowiak, Caitlin L. ; Yang, Fei ; Wu, Yun ; Wistuba, Ignacio ; Moulder, Stacy L. ; Symmans, William F. ; Scott, Kenneth L. ; Edwards, John R. ; Liang, Han ; Heffernan, Timothy P. ; Piwnica-Worms, Helen. / A functional genomic screen in vivo identifies CEACAM5 as a clinically relevant driver of breast cancer metastasis. In: npj Breast Cancer. 2018 ; Vol. 4, No. 1.
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