10P - PIM1 kinase promotes cell migration via SHP2 in triple-negative breast cancer

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cancers in Adolescents and Young Adults (AYA)
Cancer biology
Breast Cancer
Basic Scientific Principles
Presenter Fara Braso Maristany
Citation Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361
Authors F. Braso Maristany1, J. Quist1, C. Wells2, A. Grigoriadis1, P. Marra1, A. Tutt1
  • 1Breast Cancer Now Research Unit, Division Of Cancer Studies, King's College London, SE1 9RT - London/GB
  • 2Cancer Cell Biology & Imaging, Division Of Cancer Studies, King's College London, SE1 9RT - London/GB



Triple-negative breast cancers (TNBCs) are aggressive and associated with poor prognosis. We have recently demonstrated that PIM1 regulates cell death, tumour growth and chemotherapy response in TNBC. This study aims to further explore the molecular mechanisms by which PIM1 promotes malignant phenotypes in TNBC, in particular cell migration.


The HumanHT-12 v4 expression array was used to interrogate changes in gene expression upon PIM1 knockdown in TNBC cell lines. Transwell migration assays and time-lapse live-cell imaging were used to study the role of PIM1 in cell migration. To assess the morphology of TNBC cells we stained F-actin with 488-phalloidin. Phospho-kinase arrays were used to elucidate the pathway by which PIM1 may control cell migration.


Gene expression analysis revealed PTPN11 as the most downregulated gene upon PIM1 knockdown in TNBC cell lines. These results were validated by qRTPCR in 3 TNBC cell lines. PTPN11 encodes for the phosphatase SHP2, known to be relevant for the migration of TNBC cells. We therefore studied whether PIM1 was also required for this phenotype in TNBC cell lines. PIM1 knockdown led to a defect on 2D-transwell migration in MDA-MB-231 and SUM159 cells, similar to that observed upon SHP2 knockdown. Interestingly, SHP2 knockdown did not affect short-term cell population growth of TNBC cells, suggesting that PIM1 exerts its role in cell population growth via different mechanisms, as demonstrated previously. Upon PIM1 knockdown, MDA-MB-231 showed lower motility persistence, increased circularity and a reduction of F-actin filaments. To understand the common downstream targets of PIM1 and SHP2 and elucidate the pathway by which PIM1 may control cell migration, we used phospho-kinase arrays. These revealed decreased phosphorylation of PLCg1, FAK and PYK2, proteins involved in cell migration, upon either PIM1 or SHP2 knockdown.


These data suggest that PIM1 regulates cell migration by controlling PTPN11/SHP2 expression and provide further evidence for PIM1 as a target for TNBC therapy, not only to induce apoptosis and prevent tumour growth, but also to prevent TNBC migration.

Clinical trial identification


Legal entity responsible for the study

King's College London/Breast Cancer Now


Breast Cancer Now


All authors have declared no conflicts of interest.