title: Suppression of Spry1 inhibits triple-negative breast cancer malignancy by decreasing EGF/EGFR mediated mesenchymal phenotype.
abstract: Sprouty (Spry) proteins have been implicated in cancer progression, but their role in triple-negative breast cancer (TNBC), a subtype of lethal and aggressive breast cancer, is unknown. Here, we reported that Spry1 is significantly expressed in TNBC specimen and MDA-MB-231 cells. To understand Spry1 regulation of signaling events controlling breast cancer phenotype, we used lentiviral delivery of human Spry1 shRNAs to suppress Spry1 expression in MDA-MB-231, an established TNBC cell line. Spry1 knockdown MDA-MB-231 cells displayed an epithelial phenotype with increased membrane E-cadherin expression. Knockdown of Spry1 impaired MDA-MB-231 cell migration, Matrigel invasion, and anchorage-dependent and -independent growth. Tumor xenografts originating from Spry1 knockdown MDA-MB-231 cells grew slower, had increased E-cadherin expression, and yielded fewer lung metastases compared to control. Furthermore, suppressing Spry1 in MDA-MB-231 cells impaired the induction of Snail and Slug expression by EGF, and this effect was associated with increased EGFR degradation and decreased EGFR/Grb2/Shp2/Gab1 signaling complex formation. The same phenotype was also observed in the TNBC cell line MDA-MB-157. Together, our results show that unlike in some tumors, where Spry may mediate tumor suppression, Spry1 plays a selective role in at least a subset of TNBC to promote the malignant phenotype via enhancing EGF-mediated mesenchymal phenotype.
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: He
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME, USA.|Department of Respiratory Medicine, The First Hospital of Jinlin University, Changchun, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Jing
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME, USA.
authors.forename: Lucy
authors.initials: L
authors.lastname: Liaw
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME, USA.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Gower
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME, USA.
authors.forename: Calvin
authors.initials: C
authors.lastname: Vary
authors.affiliation: Department of Respiratory Medicine, The First Hospital of Jinlin University, Changchun, China.
authors.forename: Shucheng
authors.initials: S
authors.lastname: Hua
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME, USA.
authors.forename: Xuehui
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen; D004338:Drug Combinations; D004815:Epidermal Growth Factor / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007797:Laminin; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D004338:Drug Combinations; D007797:Laminin; D008565:Membrane Proteins; D010750:Phosphoproteins; D011509:Proteoglycans; C486055:SPRY1 protein, human; C059485:matrigel; D004815:Epidermal Growth Factor; D003094:Collagen; D066246:ErbB Receptors