title: Dynamic dialog between cytokeratin 18 and annexin A1 in breast cancer: a transcriptional disequilibrium.
abstract: Cytokeratins (CKs) constitute the cytoskeletal network and are regulated by post-translational modifications, acting not only as a mechanical support, but also in cell signaling and regulatory processes. Signaling is mediated by CK-associated proteins, such as Annexin A1 (ANXA1), a ligand of the CK18/CK8 complex. ANXA1 has a pivotal role in cellular and immunological responses, and together with CK18 have been implicated in several processes related to malignant transformation in breast cancer (BC). Our aim was to demonstrate how their interaction might be linked to BC development. We investigated transcript levels, protein expression and distribution for both targets in breast tissues of 92 patients (42 BCs and 50 benign diseases) using qPCR and immunohistochemistry, respectively. ANXA1 and CK18 mRNAs were inversely correlated, and their ratio in each TNM stage significantly differentiated BC from benign diseases (OR=5.62). These differences did not mirror tissue protein levels, but a significant dichotomous protein distribution in tumor tissues was observed, differing from the expected co-localization observed during cell homeostasis. The disequilibrium of transcriptional levels between ANXA1/CK18 and alterations in their tissue distribution are present either in initial events or tumor progression, which suggest a critical event in BC. The broken dialog between ANXA1 and CK18 in normal breast tissues may play a critical role in BC development, and together may be used as combined targets for BC diagnostics.
authors.affiliation: Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, MG, Brazil. Electronic address: tgaraujo@ingeb.ufu.br.
authors.forename: Thaise G
authors.initials: TG
authors.lastname: Araujo
authors.affiliation: Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, MG, Brazil.
authors.forename: Karina
authors.initials: K
authors.lastname: Marangoni
authors.affiliation: AC Camargo Cancer Hospital, São Paulo, SP, Brazil.
authors.forename: Rafael M
authors.initials: RM
authors.lastname: Rocha
authors.affiliation: School of Medicine, Federal University of Uberlandia, Uberlandia, MG, Brazil.
authors.forename: Yara C P
authors.initials: YC
authors.lastname: Maia
authors.affiliation: Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, MG, Brazil.
authors.forename: Galber R
authors.initials: GR
authors.lastname: Araujo
authors.affiliation: Department of Pathology, Clinical Hospital of Uberlandia, Federal University of Uberlandia, Uberlandia, MG, Brazil.
authors.forename: Tânia M
authors.initials: TM
authors.lastname: Alcântar
authors.affiliation: Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, MG, Brazil.
authors.forename: Patrícia T
authors.initials: PT
authors.lastname: Alves
authors.affiliation: Obstetrics Division, Internal Medicine, University Hospital, Federal University of Uberlandia, Uberlandia, MG, Brazil.
authors.forename: Luanda
authors.initials: L
authors.lastname: Calábria
authors.affiliation: Laboratory of Genetics and Biotechnology, Federal University of Goias, Catalao, GO, Brazil.
authors.forename: Adriana F
authors.initials: AF
authors.lastname: Neves
authors.affiliation: AC Camargo Cancer Hospital, São Paulo, SP, Brazil.
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, MG, Brazil; Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, USA.
authors.forename: Luiz R
authors.initials: LR
authors.lastname: Goulart
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D014158:Transcription, Genetic
chemical_list: D017305:Annexin A1; D053538:Keratin-18
keywords: Annexin A1; Breast cancer; Cytokeratin 18; Immunohistochemistry; qPCR