title: β-III tubulin modulates the behavior of Snail overexpressed during the epithelial-to-mesenchymal transition in colon cancer cells.
abstract: Class III β-tubulin (TUBB3) is a marker of drug resistance expressed in a variety of solid tumors. Originally, it was described as an important element of chemoresistance to taxanes. Recent studies have revealed that TUBB3 is also involved in an adaptive response to a microenvironmental stressor, e.g. low oxygen levels and poor nutrient supply in some solid tumors, independently of the microtubule targeting agent. Furthermore, it has been demonstrated that TUBB3 is a marker of biological aggressiveness associated with modulation of metastatic abilities in colon cancer. The epithelial-to-mesenchymal transition (EMT) is a basic cellular process by which epithelial cells lose their epithelial behavior and become invasive cells involved in cancer metastasis. Snail is a zinc-finger transcription factor which is able to induce EMT through the repression of E-cadherin expression. In the presented studies we focused on the analysis of the TUBB3 role in EMT-induced colon adenocarcinoma cell lines HT-29 and LS180. We observed a positive correlation between Snail presence and TUBB3 upregulation in tested adenocarcinoma cell lines. The cellular and behavioral analysis revealed for the first time that elevated TUBB3 level is functionally linked to increased cell migration and invasive capability of EMT induced cells. Additionally, the post-transcriptional modifications (phosphorylation, glycosylation) appear to regulate the cellular localization of TUBB3 and its phosphorylation, observed in cytoskeleton, is probably involved in cell motility modulation.
authors.affiliation: Department of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Sobierajska
authors.affiliation: Department of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland,; Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, Rzgowska 281/289, 93-338, Lodz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wieczorek
authors.affiliation: Department of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland.
authors.forename: Wojciech M
authors.initials: WM
authors.lastname: Ciszewski
authors.affiliation: Department of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Sacewicz-Hofman
authors.affiliation: Department of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland.
authors.forename: Marta E
authors.initials: ME
authors.lastname: Wawro
authors.affiliation: Department of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Wiktorska
authors.affiliation: Institute of Medical Biology, PAS, Lodowa 106, 93-232, Lodz, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Boncela
authors.affiliation: Institute of Medical Biology, PAS, Lodowa 106, 93-232, Lodz, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Papiewska-Pajak
authors.affiliation: Nencki Institute of Experimental Biology, PAS, Pasteura 3, 02-093, Warsaw, Poland, Institute of Medical Biology, PAS, Lodowa 106, 93-232, Lodz, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Kwasniak
authors.affiliation: Nencki Institute of Experimental Biology, PAS, Pasteura 3, 02-093, Warsaw, Poland, Institute of Medical Biology, PAS, Lodowa 106, 93-232, Lodz, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Wyroba
authors.affiliation: Institute of Medical Biology, PAS, Lodowa 106, 93-232, Lodz, Poland; Department of Molecular and Medical Biophysics, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland.
authors.forename: Czeslaw S
authors.initials: CS
authors.lastname: Cierniewski
authors.affiliation: Department of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland,. Electronic address: jolanta.niewiarowska@umed.lodz.pl.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Niewiarowska
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D002451:Cell Compartmentation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D019073:HT29 Cells; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D000071250:Snail Family Transcription Factors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; C498585:TUBB3 protein, human; D053773:Transforming Growth Factor beta1; D014404:Tubulin
keywords: Colon cancer; EMT; Migration; Snail; β-III tubulin