title: CIP4 promotes metastasis in triple-negative breast cancer and is associated with poor patient prognosis.
abstract: Signaling via epidermal growth factor receptor (EGFR) and Src kinase pathways promote triple-negative breast cancer (TNBC) cell invasion and tumor metastasis. Here, we address the role of Cdc42-interacting protein-4 (CIP4) in TNBC metastasis in vivo, and profile CIP4 expression in human breast cancer patients. In human TNBC cells, CIP4 knock-down (KD) led to less sustained activation of Erk kinase and impaired cell motility compared to control cells. This correlated with significant defects in 3D invasion of surrounding extracellular matrix by CIP4 KD TNBC cells when grown as spheroid colonies. In mammary orthotopic xenograft assays using both human TNBC cells (MDA-MB-231, HCC 1806) and rat MTLn3 cells, CIP4 silencing had no overt effect on tumor growth, but significantly reduced the incidence of lung metastases in each tumor model. In human invasive breast cancers, high CIP4 levels was significantly associated with high tumor stage, TNBC and HER2 subtypes, and risk of progression to metastatic disease. Together, these results implicate CIP4 in promoting metastasis in TNBCs.
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Otto L D
authors.initials: OL
authors.lastname: Cerqueira
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, and Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Kingston, ON, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Truesdell
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, and Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Kingston, ON, Canada.
authors.forename: Tomas
authors.initials: T
authors.lastname: Baldassarre
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Santiago A
authors.initials: SA
authors.lastname: Vilella-Arias
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, and Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Kingston, ON, Canada.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Watt
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, and Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Kingston, ON, Canada.
authors.forename: Jalna
authors.initials: J
authors.lastname: Meens
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, and Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Kingston, ON, Canada.
authors.forename: Harish
authors.initials: H
authors.lastname: Chander
authors.affiliation: Department of Anatomic Pathology, A.C. Camargo Hospital, São Paulo, SP, Brazil.
authors.forename: Cynthia A B
authors.initials: CA
authors.lastname: Osório
authors.affiliation: Department of Anatomic Pathology, A.C. Camargo Hospital, São Paulo, SP, Brazil.|Instituto Nacional de Ciência e Tecnologia em Oncogenômica, São Paulo, SP, Brazil.
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.|Instituto Nacional de Ciência e Tecnologia em Oncogenômica, São Paulo, SP, Brazil.
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Reis
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, and Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Kingston, ON, Canada.
authors.forename: Andrew W B
authors.initials: AW
authors.lastname: Craig
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D051381:Rats; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
chemical_list: D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; C406285:TRIP10 protein, human
keywords: CIP4; metastasis; triple-negative breast cancer
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