Autocrine production of interleukin-4 and interleukin-10 is required for survival and growth of thyroid cancer cells.
AbstractAlthough CD95 and its ligand are expressed in thyroid cancer, the tumor cell mass does not seem to be affected by such expression. We have recently shown that thyroid carcinomas produce interleukin (IL)-4 and IL-10, which promote resistance to chemotherapy through the up-regulation of Bcl-xL. Here, we show that freshly purified thyroid cancer cells were completely refractory to CD95-induced apoptosis despite the consistent expression of Fas-associated death domain and caspase-8. The analysis of potential molecules able to prevent caspase-8 activation in thyroid cancer cells revealed a remarkable up-regulation of cellular FLIPL (cFLIPL) and PED/PEA-15, two antiapoptotic proteins whos…
Structure‐ and Interaction‐Based Design of Anti‐SARS‐CoV‐2 Aptamers
Aptamer selection against novel infections is a complicated and time-consuming approach. Synergy can be achieved by using computational methods together with experimental procedures. This study aims to develop a reliable methodology for a rational aptamer in silico et vitro design. The new approach combines multiple steps: (1) Molecular design, based on screening in a DNA aptamer library and directed mutagenesis to fit the protein tertiary structure; (2) 3D molecular modeling of the target; (3) Molecular docking of an aptamer with the protein; (4) Molecular dynamics (MD) simulations of the complexes; (5) Quantum-mechanical (QM) evaluation of the interactions between aptamer and target with …
PED is overexpressed and mediates TRAIL resistance in human non-small cell lung cancer
PED (phosphoprotein enriched in diabetes) is a death-effector domain (DED) family member with a broad anti-apoptotic action. PED inhibits the assembly of the death-inducing signalling complex (DISC) of death receptors following stimulation. Recently, we reported that the expression of PED is increased in breast cancer cells and determines the refractoriness of these cells to anticancer therapy. In the present study, we focused on the role of PED in non-small cell lung cancer (NSCLC), a tumour frequently characterized by evasion of apoptosis and drug resistance. Immunohistochemical analysis of a tissue microarray, containing 160 lung cancer samples, indicated that PED was strongly expressed …
MiR-221 promotes stemness of breast cancer cells by targeting DNMT3b
// Giuseppina Roscigno 1, 2 , Cristina Quintavalle 1, 2 , Elvira Donnarumma 3 , Ilaria Puoti 1 , Angel Diaz-Lagares 4 , Margherita Iaboni 1 , Danilo Fiore 1 , Valentina Russo 1 , Matilde Todaro 5 , Giulia Romano 6 , Renato Thomas 7 , Giuseppina Cortino 7 , Miriam Gaggianesi 5 , Manel Esteller 4 , Carlo M. Croce 6 , Gerolama Condorelli 1, 2 1 Department of Molecular Medicine and Medical Biotechnology, “Federico II” University of Naples, Naples, Italy 2 IEOS-CNR, Naples, Italy 3 IRCCS-SDN, Naples, Italy 4 Epigenetic and Cancer Biology Program (PEBC) IDIBELL, Hospital Duran I Reynals, Barcelona, Spain 5 Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Lab…
PED Mediates AKT-Dependent Chemoresistance in Human Breast Cancer Cells
Abstract Killing of tumor cells by cytotoxic therapies, such as chemotherapy or gamma-irradiation, is predominantly mediated by the activation of apoptotic pathways. Refractoriness to anticancer therapy is often due to a failure in the apoptotic pathway. The mechanisms that control the balance between survival and cell death in cancer cells are still largely unknown. Tumor cells have been shown to evade death signals through an increase in the expression of antiapoptotic molecules or loss of proapoptotic factors. We aimed to study the involvement of PED, a molecule with a broad antiapoptotic action, in human breast cancer cell resistance to chemotherapeutic drugs–induced cell death. We show…
MiR-24 induces chemotherapy resistance and hypoxic advantage in breast cancer
// Giuseppina Roscigno 1, 2, * , Ilaria Puoti 1, 2, * , Immacolata Giordano 1 , Elvira Donnarumma 3 , Valentina Russo 1 , Alessandra Affinito 1 , Assunta Adamo 1 , Cristina Quintavalle 1, 2 , Matilde Todaro 4 , Maria dM Vivanco 5 , Gerolama Condorelli 1, 2 1 Department of Molecular Medicine and Medical Biotechnology, “Federico II” University of Naples, Naples, Italy 2 IEOS, CNR, Naples, Italy 3 IRCCS-SDN, Naples, Italy 4 Department of Pathobiology and Medical Biotechnology, University of Palermo, Palermo, Italy 5 CIC bioGUNE, Centre for Cooperative Research in Biosciences, Derio, Spain * These authors have contributed equally to the paper as first authors Correspondence to: Gerolama Condore…
Highly Homogeneous Biotinylated Carbon Nanodots: Red-Emitting Nanoheaters as Theranostic Agents toward Precision Cancer Medicine
Very recent red-emissive carbon nanodots (CDs) have shown potential as near-infrared converting tools to produce local heat useful in cancer theranostics. Besides, CDs seem very appealing for clinical applications combining hyperthermia, imaging, and drug delivery in a single platform capable of selectively targeting cancer cells. However, CDs still suffer from dramatic dot-to-dot variability issues such that a rational design of their structural, optical, and chemical characteristics for medical applications has been impossible so far. Herein, we report for the first time a simple and highly controllable layer-by-layer synthesis of biotin-decorated CDs with monodisperse size distribution, …
Apoptosis resistance in epithelial tumors is mediated by tumor-cell-derived interleukin-4
We investigated the mechanisms involved in the resistance to cell death observed in epithelial cancers. Here, we identify that primary epithelial cancer cells from colon, breast and lung carcinomas express high levels of the antiapoptotic proteins PED, cFLIP, Bcl-xL and Bcl-2. These cancer cells produced interleukin-4 (IL-4), which amplified the expression levels of these antiapoptotic proteins and prevented cell death induced upon exposure to TRAIL or other drug agents. IL-4 blockade resulted in a significant decrease in the growth rate of epithelial cancer cells and sensitized them, both in vitro and in vivo, to apoptosis induction by TRAIL and chemotherapy via downregulation of the antia…