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Identifier

000423825

Title

Interplay between the cell polarity protein Scrib and signaling proteins in breast cancer

Alternative Title

Συνεργασία της πρωτεΐνης κυτταρικής πολικότητας SCRIB και σηματοδοτικών πρωτεϊνών στον καρκίνο του μαστού

Author

Μακκού, Μαρία Π.

Thesis advisor

Παπαματθαιάκης, Ιωσήφ

Abstract

Cell polarity is fundamental for the architecture and function of all body tissues by determining crucial cellular functions such as asymmetric cell division and cell migration. Normal epithelial cells are a typical example of polarized cells (apico-basal polarity) with the apical surface exposed to the lumen and the basal surface attached to the basement membrane. Three main protein complexes are responsible for the establishment of cell polarity, the Crumbs (Crumbs3-PALS1-PATJ) and Par (Par3-Par6-aPKC) complexes identify the apical domain of the cell, while the Scribble complex [lethal giant larvae (Lgl) - Scribble (Scrib) - Disc large (Dlg)] defines the basal domain. In epithelial cells, polarity proteins are recruited at intercellular connections where they associate with adhesion proteins as well as other proteins, components of signaling pathways that regulate cell growth, differentiation, apoptosis and epithelial-mesenchymal transition (EMT). Alterations of Scrib polarity gene structure or regulation that leads to abnormal protein levels or subcellular localization due to various point mutations or gene amplification have been observed in several cases of cancer. Scrib has been found to act synergistically with activated oncogenic signaling pathways such as Ras, ErbB2 and TGFβ to promote tumor formation and metastasis. This study unveils a role for a truncated form of Scrib that has been found in several cancers, in regulating mTOR, Wnt and JNK signaling in human breast cancer cell lines. Overall, this study defines the truncated Scrib94-494 as a major regulator of signaling events with executive role in apoptotic cell death and cell invasion.

Language

English

Subject

JNK

Wnt

mTOR

Issue date

2019-12-05

Collection

School/Department--School of Sciences and Engineering--Department of Biology--Doctoral theses

Type of Work--Doctoral theses

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