PBF phosphorylation regulates cell motility of thyroid and breast cancer cells

Merve Kocbiyik, Mohammed Alshahrani, Vikki Poole, Sakaorna Jeyanathan, Caitlin Thornton, Ling Zha, Katie Brookes, Hannah Nieto, Martin Read, Christopher McCabe, Vicki Smith

Research output: Contribution to journalAbstractpeer-review

Abstract

The proto-oncogene pituitary tumor transforming gene binding factor (PTTG1IP/PBF) is overexpressed in multiple tumours and associated with tumour progression. One of the tumourigenic processes that PBF can mediate is cell motility. PBF can induce cell invasion in both thyroid and breast cancer cell lines. However, in contrast to wild-type (WT) PBF, the Y174A PBF mutant was not able to induce the invasiveness of thyroid or breast cancer cells. The Y174 residue is highly phosphorylated and these findings implicated that phosphorylation mediates the induction of breast and thyroid cancer cell invasion by PBF. Mutation of Y174 also causes retention of PBF at the plasma membrane due to disruption of an endocytosis motif. To better understand the impact of PBF phosphorylation and localisation on cell motility, a mutant with a disrupted Src consensus sequence (EEN170-172AAA;‘PBF-EEN’) and another with a substitution at F177 (F177A) were also employed. PBF-EEN shows largely vesicular localisation, similar to WT PBF, but with reduced phosphorylation. F177A accumulates at the plasma membrane due to the disruption of the endocytosis motif but is still phosphorylated. Our preliminary data again demonstrate significant induction of cell migration with PBF overexpression using both scratch wound and Transwell migration assays in thyroid and breast cancer cells. In contrast, neither Y174A, PBF-EEN nor F177A were able to stimulate cell migration. This further suggests that PBF phosphorylation is important for PBF induction of cell motility and also suggests that the endocytosis of PBF is essential. This study provides more insight into the mechanism of PBF induction of cell motility and supports PBF pY174 as a potential therapeutic target. Understanding the impact of PBF phosphorylation may help to develop new treatment approaches for cancer progression.
Original languageEnglish
Article numberOC2.4
Number of pages1
JournalEndocrine Abstracts
Volume77
DOIs
Publication statusPublished - 8 Nov 2021

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