Profilin-1 deficiency leads to SMAD3 upregulation and impaired 3D outgrowth of breast cancer cells.

Adhesion-mediated activation of FAK/ERK signalling pathway, enabled by the formation of filopodial protrusions (FLP), has been shown to be an important event for triggering of dormancy-to-proliferation switch and metastatic outgrowth of breast cancer cells (BCC). We studied the role of actin-binding protein profilin1 (Pfn1) in these processes. Quantitative immunohistochemistry (IHC) of BC tissue microarray (TMA) and survival analyses of curated transcriptome datasets of BC patients were performed to examine Pfn1's association with certain clinicopathological features. FLP formation and single cell outgrowth of BCC were assessed using a 3D matrigel culture that accurately predicts dormant vs metastatic outgrowth phenotypes of BCC in certain microenvironment. Gene expression studies were performed to identify potential biological pathways that are perturbed under Pfn1-depleted condition. Lower Pfn1 expression is correlated with lower nuclear grade of breast tumours and longer relapse-free survival of BC patients. Pfn1 depletion leads to defects in FLP and outgrowth of BCC but without impairing either FAK or ERK activation. Guided by transcriptome analyses, we further showed that Pfn1 depletion is associated with prominent SMAD3 upregulation. Although knockdown and overexpression experiments revealed that SMAD3 has an inhibitory effect on the outgrowth of breast cancer cells, SMAD3 knockdown alone was not sufficient to enhance the outgrowth potential of Pfn1-depleted BCC suggesting that other proliferation-regulatory pathways in conjunction with SMAD3 upregulation may underlie the outgrowth-deficient phenotype of BCC cells upon depletion of Pfn1. Overall, these data suggest that Pfn1 may be a novel biomarker for BC recurrence and a possible target to reduce metastatic outgrowth of BCC

(Blue) Growth accounting in small-scale European Union fleets

Fisheries account for one-third of the total jobs in the global ocean economies. Small scale fleets (SSF) fisheries are the main segment from the number of jobs point of view, and in the EU, SSF account for over 40% of employment in the fisheries sector. Given this marine employment source, it is important to analyse SSF's productivity growth. This was done using Total Factor Productivity (TFP), which is dened as the portion of output not explained by the traditionally measured inputs of labour, energy and capital used in production. TFP calculation is relevant to understand the technology evolution in fisheries and as a reference for management assessment. TFP was calculated for SSF in two EU main sea areas, the Mediterranean (FAO area 37) and the North-East Atlantic (FAO area 27). Constant elasticity production functions were used to analyse the intensity of the use of production factors and how these are substituted or complemented when producing. Additionally, TFP was corrected by stock evolution indexes to evaluate the EU conservation policy. Results showed how the TFP presented signs of stagnation when stocks status were considered. This implies a low technological evolution and that the use of production factors is to be reduced in the following years. It was concluded that in the North-East Atlantic the EU conservation policy is obtaining the objective of restoring fish stocks and contributing to maintaining the productivity. In the Mediterranean, the stocks are not being restored, therefore not contributing to growth as a production factor. Finally, it is concluded that in neither areas the conservation policy is enough to provide positive productivity trends.JRC.D.2-Water and Marine Resource