title: Myosin 1e promotes breast cancer malignancy by enhancing tumor cell proliferation and stimulating tumor cell de-differentiation.
abstract: Despite advancing therapies, thousands of women die every year of breast cancer. Myosins, actin-dependent molecular motors, are likely to contribute to tumor formation and metastasis via their effects on cell adhesion and migration and may provide promising new targets for cancer therapies. Using the MMTV-PyMT murine model of breast cancer, we identified Myosin 1e (MYO1E) as a novel tumor promoter. Tumor latency in mice lacking MYO1E was significantly increased, and tumors formed in the absence of MYO1E displayed unusual papillary morphology, with well-differentiated layers of epithelial cells covering fibrovascular cores, rather than solid sheets of tumor cells typically observed in this cancer model. These tumors were reminiscent of papillary breast cancer in humans that is typically non-invasive and often cured by tumor excision. MYO1E-null tumors exhibited decreased expression of the markers of cell proliferation, which was recapitulated in primary tumor cells derived from MYO1E-null mice. In agreement with our findings, meta-analysis of patient survival data indicated that MYO1E expression level was associated with reduced recurrence-free survival in basal-like breast cancer. Overall, our data suggests that MYO1E contributes to breast tumor malignancy and regulates the differentiation and proliferation state of breast tumor cells.
authors.affiliation: Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Ouderkirk-Pecone
authors.affiliation: Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Goreczny
authors.affiliation: Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Chase
authors.affiliation: Department of Pathology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Arthur H
authors.initials: AH
authors.lastname: Tatum
authors.affiliation: Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Turner
authors.affiliation: Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Mira
authors.initials: M
authors.lastname: Krendel
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D054337:Cell Dedifferentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024461:Myosin Type I; D009218:Myosins / Q000378:metabolism*; D011379:Prognosis
chemical_list: C505821:Myo1e protein, mouse; D024461:Myosin Type I; D009218:Myosins
keywords: animal models of cancer; breast cancer; myosin; therapeutic targets; tumor promotion and progression