Related Experiment Video
Updated: Mar 15, 2026
Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts
Published on: August 27, 2012
Pro-invasive Effect of Proto-oncogene PBF Is Modulated by an Interaction with Cortactin
Rachel J Watkins1, Waraporn Imruetaicharoenchoke1, Martin L Read1
1Institute of Metabolism and Systems Research (R.J.W., W.I., M.L.R., N.S., V.L.P., S.B., R.F., H.R.N., K.B., V.E.S., C.J.M.), University of Birmingham, Birmingham B15 2TT, United Kingdom; Department of Surgery, Faculty of Medicine (W.I.), Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; Section of Endocrinology and Internal Medicine (E.G.), University of Ferrara, 44121 Ferrara, Italy; STIM Laboratory (E.B.), University of Poitiers, 86073 Poitiers Cedex 9, France; Northern Centre for Cancer Care (U.M.), Freeman Hospital, Newcastle upon Tyne NE7 7DN, United Kingdom; Cancer Research United Kingdom & UCL Cancer Trials Centre (A.H.), University College London, London WC1E 6BT, United Kingdom; and Institute of Cancer and Genomic Sciences (H.M.), University of Birmingham, Birmingham B15 2TT, United Kingdom.
Context:
Metastatic disease is responsible for the majority of endocrine cancer deaths. New therapeutic targets are urgently needed to improve patient survival rates.
Objective:
The proto-oncogene PTTG1-binding factor (PBF/PTTG1IP) is overexpressed in multiple endocrine cancers and circumstantially associated with tumor aggressiveness. This study aimed to understand the role of PBF in tumor cell invasion and identify possible routes to inhibit its action. Design, Setting, Patients, and Interventions: Thyroid, breast, and colorectal cells were transfected with PBF and cultured for in vitro analysis. PBF and cortactin (CTTN) expression was determined in differentiated thyroid cancer and The Cancer Genome Atlas RNA-seq data.
Primary Outcome Measure:
Pro-invasive effects of PBF were evaluated by 2D Boyden chamber, 3D organotypic, and proximity ligation assays.
Results:
Our study identified that PBF and CTTN physically interact and co-localize, and that this occurs at the cell periphery, particularly at the leading edge of migrating cancer cells. Critically, PBF induces potent cellular invasion and migration in thyroid and breast cancer cells, which is entirely abrogated in the absence of CTTN. Importantly, we found that CTTN is over-expressed in differentiated thyroid cancer, particularly in patients with regional lymph node metastasis, which significantly correlates with elevated PBF expression. Mutation of PBF (Y174A) or pharmacological intervention modulates the PBF: CTTN interaction and attenuates the invasive properties of cancer cells.
Conclusion:
Our results demonstrate a unique role for PBF in regulating CTTN function to promote endocrine cell invasion and migration, as well as identify a new targetable interaction to block tumor cell movement.
Related Concept Videos
01:35Cancer Cell Migration through Invadopodia
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
02:23Abnormal Proliferation
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:33Cancer-Critical Genes I: Proto-oncogenes
02:38The Ras Gene
Ras is a...