title: Elevated expression of myosin X in tumours contributes to breast cancer aggressiveness and metastasis.
abstract: BACKGROUND
  Myosin X (MYO10) was recently reported to promote tumour invasion by transporting integrins to filopodial tips in breast cancer. However, the role of MYO10 in tumours remains poorly defined. Here, we report that MYO10 is required in invadopodia to mediate invasive growth and extracellular matrix degradation, which depends on the binding of MYO10's pleckstrin homology domain to PtdIns(3,4,5)P3.
  
  
  METHODS
  The expression of MYO10 and its associations with clinicopathological and biological factors were examined in breast cancer cells and breast cancer specimens (n=120). Cell migration and invasion were investigated after the silencing of MYO10. The ability of cells to form invadopodia was studied using a fluorescein isothiocyanate-conjugated gelatin degradation assay. A mouse model was established to study tumour invasive growth and metastasis in vivo.
  
  
  RESULTS
  Elevated MYO10 levels were correlated with oestrogen receptor status, progesterone receptor status, poor differentiation, and lymph node metastasis. Silencing MYO10 reduced cell migration and invasion. Invadopodia were responsible for MYO10's role in promoting invasion. Furthermore, decreased invasive growth and lung metastasis were observed in the MYO10-silenced nude mouse model.
  
  
  CONCLUSIONS
  Our findings suggest that elevated MYO10 expression increases the aggressiveness of breast cancer; this effect is dependent on the involvement of MYO10 in invadopodial formation.
authors.affiliation: Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin Province, China 130024.
authors.forename: R
authors.initials: R
authors.lastname: Cao
authors.affiliation: Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin Province, China 130024.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin Province, China 130024.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin Province, China 130024.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin Province, China 130024.
authors.forename: X
authors.initials: X
authors.lastname: Qing
authors.affiliation: Sino-Japanese Friendship Hospital, Jilin University, 126 Xiantai Street, Changchun, Jilin Province, China 130033.
authors.forename: W
authors.initials: W
authors.lastname: Xing
authors.affiliation: Sino-Japanese Friendship Hospital, Jilin University, 126 Xiantai Street, Changchun, Jilin Province, China 130033.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin Province, China 130024.
authors.forename: Y S
authors.initials: YS
authors.lastname: Malik
authors.affiliation: Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin Province, China 130024.
authors.forename: H
authors.initials: H
authors.lastname: Yu
authors.affiliation: Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin Province, China 130024.
authors.forename: X
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D022081:Cell Surface Extensions; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000556:secondary; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009218:Myosins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C498718:MYO10 protein, human; D018129:Phosphatidylinositol Phosphates; D034741:RNA, Small Interfering; C060974:phosphatidylinositol 3,4,5-triphosphate; D009218:Myosins