Radiation therapy affects YAP expression and intracellular localization by modulating lamin A/C levels in breast cancer

The microenvironment of breast cancer actively participates in tumorigenesis and cancer progression. The changes observed in the architecture of the extracellular matrix initiate an oncogene-mediated cell reprogramming, that leads to a massive triggering of YAP nuclear entry, and, therefore, to cancer cell proliferation, invasion and probably to increased radiation-resistance. However, it is not yet fully understood how radiotherapy regulates the expression and subcellular localization of YAP in breast cancer cells experiencing different microenvironmental stiffnesses. To elucidate the role of extracellular matrix stiffness and ionizing radiations on YAP regulation, we explored the behaviour of two different mammary cell lines, a normal epithelial cell line (MCF10A) and a highly aggressive and invasive adenocarcinoma cell line (MDA-MB-231) interacting with polyacrylamide substrates mimicking the mechanics of both normal and tumour tissues (~1 and ~13 kPa). We report that X-ray radiation affected in a significant way the levels of YAP expression, density, and localization in both cell lines. After 24 h, MCF10A and MDA-MB231 increased the expression level of YAP in both nucleus and cytoplasm in a dose dependent manner and particularly on the stiffer substrates. After 72 h, MCF10A reduced mostly the YAP expression in the cytoplasm, whereas it remained high in the nucleus of cells on stiffer substrates. Tumour cells continued to exhibit higher levels of YAP expression, especially in the cytoplasmic compartment, as indicated by the reduction of nuclear/ cytoplasmic ratio of total YAP. Then, we investigated the existence of a correlation between YAP localization and the expression of the nuclear envelope protein lamin A/C, considering its key role in modulating nuclear deformability and changes in YAP shuttling phenomena. As supposed, we found that the effects of radiation on YAP nucleus/cytoplasmic expression ratio, increasing in healthy cells and decreasing in tumour ones, were accompanied by lower and higher lamin A/C levels in MCF10A and MDAMB-231 cells, respectively. These findings point to obtain a deeper knowledge of the role of the extracellular matrix and the effects of X-rays on YAP and lamin A/C expression that can be used in the design of doses and timing of radiation therapy

Investigation of Biophysical Migration Parameters for Normal Tissue and Metastatic Cancer Cells After Radiotherapy Treatment

A large body of literature has demonstrated that the mechanical properties of microenvironment have a key role in regulating cancer cell adhesion, motility, and invasion. In this work, we have introduced two additional parameters, named cell trajectory extension and area traveled by cell, to describe the tendency of normal tissue and metastatic cancer cells to move in a directional way when they interact with physio-pathological substrates, characterized by stiffnesses of 1–13 kPa, before and after treatment with 2 doses of X-rays (2 and 10 Gy). We interpreted these data by evaluating also the impact of substrate stiffness on 2 morphological parameters which indicate not only the state of cell adhesion, but also cell polarization, prerequisite to directional movement, and the formation of protrusions over cell perimeters. We believe that a so wide analysis can give an efficient and easily readable overview of effects of radiation therapy on cell-ECM crosstalk when used as therapeutic agent

Reaction dynamics studies for the system 7Be + 208Pb at Coulomb barrier energies

The scattering process of the Radioactive Ion Beam 7Be from a 208Pb target was measured at three near-barrier energies. The quasi-elastic angular distributions were analyzed within the framework of the optical model to extract the reaction cross sections. The results are compared with those obtained for the reactions induced by the mirror projectile 7Li and by the lightest particle-stable lithium isotope 6Li on the same target. The angular distributions for the production of the two 7Be constituent clusters, namely 3He and 4He, were also measured. In agreement with what observed for the interaction of 7Be with lighter targets, the production of the heavier helium isotope resulted to be much more abundant than that of its lighter counterpart

Evidence of dynamical dipole excitation in the fusion-evaporation of the 40Ca +152Sm heavy system

The excitation of the dynamical dipole mode along the fusion path was investigated for the first time in the formation of a heavy compound nucleus in the A ∼ 190 mass region. The compound nucleus was formed at identical conditions of excitation energy and spin from two entrance channels: the charge-asymmetric 40 Ca + 152 Sm and the nearly charge-symmetric 48 Ca + 144 Sm at E lab = 11 and 10.1 MeV / nucleon, respectively. High-energy γ rays and light charged particles were measured in coincidence with evaporation residues by means of the MEDEA multidetector array (Laboratori Nazionali del Sud, Italy) coupled to four parallel plate avalanche counters. The charged particle multiplicity spectra and angular distributions were used to pin down the average excitation energy, the average mass, and the average charge of the compound nucleus. The γ -ray multiplicity spectrum and angular distribution related to the nearly charge-symmetric channel were employed to obtain new data on the giant dipole resonance in the compound nucleus. The dynamical dipole mode excitation in the charge-asymmetric channel was evidenced, in a model-independent way, by comparing the γ -ray multiplicity spectra and angular distributions of the two entrance channels with each other. Calculations of the dynamical dipole mode in the 40 Ca + 152 Sm channel, based on a collective bremsstrahlung analysis of the reaction dynamics, are presented. Possible interesting implications in the superheavy-element quest are discussed