title: Tumor Budding: The Name is EMT. Partial EMT.
abstract: Tumor budding is a histological phenomenon encountered in various cancers, whereby individual malignant cells and/or small clusters of malignant cells are seen in the tumor stroma. Postulated to be mirror epithelial-mesenchymal transition, tumor budding has been associated with poor cancer outcomes. However, the vast heterogeneity in its exact definition, methodology of assessment, and patient stratification need to be resolved before it can be routinely used as a standardized prognostic feature. Here, we discuss the heterogeneity in defining and assessing tumor budding, its clinical significance across multiple cancer types, and its prospective implementation in clinical practice. Next, we review the emerging evidence about partial, rather than complete, epithelial-mesenchymal phenotype at the tumor bud level, and its connection with tumor proliferation, quiescence, and stemness. Finally, based on recent literature, indicating a co-expression of epithelial and mesenchymal markers in many tumor buds, we posit tumor budding to be a manifestation of this hybrid epithelial/mesenchymal phenotype displaying collective cell migration.
authors.affiliation: Departments of BioSciences, Rice University, Houston, TX 77005-1827, USA. Alexandru.Dan.Grigore@rice.edu.|Center for Theoretical Biological Physics, Rice University, Houston, TX 77005-1827, USA. Alexandru.Dan.Grigore@rice.edu.
authors.forename: Alexandru Dan
authors.initials: AD
authors.lastname: Grigore
authors.affiliation: Departments of Bioengineering, Rice University, Houston, TX 77005-1827, USA. mkjolly.15@gmail.com.|Center for Theoretical Biological Physics, Rice University, Houston, TX 77005-1827, USA. mkjolly.15@gmail.com.
authors.forename: Mohit Kumar
authors.initials: MK
authors.lastname: Jolly
authors.affiliation: Center for Theoretical Biological Physics, Rice University, Houston, TX 77005-1827, USA. dyajia@gmail.com.|Graduate Program in Systems, Synthetic and Physical Biology, Rice University, Houston, TX 77005-1827, USA. dyajia@gmail.com.
authors.forename: Dongya
authors.initials: D
authors.lastname: Jia
authors.affiliation: Departments of BioSciences, Rice University, Houston, TX 77005-1827, USA. farachca@rice.edu.|Departments of Bioengineering, Rice University, Houston, TX 77005-1827, USA. farachca@rice.edu.|Center for Theoretical Biological Physics, Rice University, Houston, TX 77005-1827, USA. farachca@rice.edu.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Farach-Carson
authors.affiliation: Departments of BioSciences, Rice University, Houston, TX 77005-1827, USA. Herbert.Levine@rice.edu.|Departments of Bioengineering, Rice University, Houston, TX 77005-1827, USA. Herbert.Levine@rice.edu.|Departments of Physics and Astronomy, Rice University, Houston, TX 77005-1827, USA. Herbert.Levine@rice.edu.|Center for Theoretical Biological Physics, Rice University, Houston, TX 77005-1827, USA. Herbert.Levine@rice.edu.
authors.forename: Herbert
authors.initials: H
authors.lastname: Levine
keywords: EMT; cancer; epithelial-mesenchymal transition; tumor budding