Valentina De Falco

Valentina De Falco
Italian National Research Council | CNR · Institute Experimental Endocrinology and Oncology "Gaetano Salvatore" IEOS

BD, PhD

About

45
Publications
4,576
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1,892
Citations
Citations since 2016
8 Research Items
600 Citations
2016201720182019202020212022020406080100120
2016201720182019202020212022020406080100120
2016201720182019202020212022020406080100120
2016201720182019202020212022020406080100120
Additional affiliations
April 2012 - February 2015
University of Naples Federico II
Position
  • Researcher

Publications

Publications (45)
Article
Full-text available
Background: Improvement in genetic characterization of Colon Cancer (CC) patients is required to propose new potential targets, since surgical resection coupled to chemotherapy, presents several limits such as cancer recurrence and drug resistance. Targeted therapies have more efficacy and less toxicity than standard treatments. One of the most re...
Article
Full-text available
In the publication of this article [1], there is an error in Fig. 7. The minus and plus signals are inverted which impairs understanding of the results described.
Article
RET receptor tyrosine kinase acts as a mutated oncogenic driver in several human malignancies and it is over-expressed in other cancers. Small molecule compounds with RET tyrosine kinase inhibitory activity are being investigated for the targeted treatment of these malignancies. Multi-targeted compounds with RET inhibitory concentration in the nano...
Article
Oncogenic conversion of the RET (rearranged during transfection) tyrosine kinase is associated with several cancers. A fragment-based chemical screen led to the identification of a novel RET inhibitor, Pz-1. Modeling and kinetic analysis identified Pz-1 as a type II tyrosine kinase inhibitor that is able to bind the “DFG-out” conformation of the ki...
Article
The inhibitory powers of a next-generation inhibitor were carefully balanced so that it is equally potent on the RET kinase and VEGFR2. In their Communication on page 8717 ff., H.-y. Li, M. Santoro, et al. report the optimization of a dual inhibitor for the treatment of RET-driven malignancies through synergistic medicinal chemistry. The inhibitor...
Article
Oncogenic conversion of the RET (rearranged during transfection) tyrosine kinase is associated with several cancers. A fragment-based chemical screen led to the identification of a novel RET inhibitor, Pz-1. Modeling and kinetic analysis identified Pz-1 as a type II tyrosine kinase inhibitor that is able to bind the "DFG-out" conformation of the ki...
Article
Full-text available
Both experimental and clinical studies suggest that any potential treatment of polycystic kidney disease should start early and last for a long time to be effective, with unavoidable side reactions and considerable costs. The aim of the present study was to test how low-doses of Rapamycin (RAPA, 0.15 mg/Kg/4 days a week i.p.), Tolvaptan (TOLV, 0.00...
Article
Full-text available
Calcium/calmodulin dependent kinase II (CaMKII) is involved in the regulation of cell proliferation. Its endogenous inhibitor (hCaKIINα) is expressed in some cell types. We determined the role of CaMKII in RET-stimulated proliferation and hCaMKIINα in medullary thyroid carcinoma (MTC). Experimental design: We analyzed the role of RET mutants on CaM...
Article
Recent studies demonstrated that the calcium/calmodulin dependent kinase 2 (CaMKII) is involved in the regulation of proliferation and survival of epithelial cells, were it phosphorylates RAF-1 and modulates MAPK pathway. A endogenous CaMKII inhibitor (hCaKIINα) is expressed in some cell types. It is down-expressed in colon and in ovarian cancer wh...
Article
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Context: The RET tyrosine kinase encoding gene acts as a dominantly transforming oncogene in thyroid carcinoma and other malignancies. Ponatinib (AP24534) is an oral ATP-competitive tyrosine kinase inhibitor that is in advanced clinical experimentation in leukemia. Objective: We tested whether ponatinib inhibited RET kinase and oncogenic activit...
Article
Full-text available
XB130, a novel adaptor protein, mediates RET/PTC chromosome rearrangement-related thyroid cancer cell proliferation and survival through phosphatidyl-inositol-3-kinase (PI3K)/Akt pathway. Recently, XB130 was found in different cancer cells in the absence of RET/PTC. To determine whether RET/PTC is required of XB130-related cancer cell proliferation...
Data
Down-regulation of XB130 with siRNA did not affect apoptosis in A549 cells in the presence of 10% FBS. A549 cells were cultured in DMEB plus 10% FBS. (A) Down-regulation of XB130 didn’t enhance spontaneous and induced cell death. A549 cells were treated with 200 nM STS, or 500 ng/ml FasAb for 24 h. (B) FasAb (500 ng/ml) with IFN-γ (100 ng/ml) did n...
Data
Phosphorylation levels of Src and MAPKs in WRO and A549 cells transfected with control or XB130 siRNA. Phosphorylations of Src, ERK and JNK were not affected by down-regulation of XB130 in WRO and A549 cells, whereas phosphrylation of p38 was increase in WRO cells. n = 4. Analyses were performed by western blotting. Mean ± SEM. *p<0.05 (compared wi...
Article
Full-text available
CD44 is a marker of cancer stem-like cells and epithelial-mesenchymal transition that is overexpressed in many cancer types, including thyroid carcinoma. At extracellular and intramembranous domains, CD44 undergoes sequential metalloprotease- and γ-secretase-mediated proteolytic cleavage, releasing the intracellular protein fragment CD44-ICD, which...
Article
The oncogenic BRAF(V600E) mutation results in an active structural conformation characterized by greatly elevated ERK activity. However, additional cellular effects caused by subcellular action of BRAF(V600E) remain to be identified. To explore these effects, differences in the subcellular localization of wild-type and mutant BRAF in thyroid cancer...
Article
Full-text available
Oncogenic conversion of the RET tyrosine kinase is a frequent feature of medullary thyroid carcinoma (MTC). ZD6474 (vandetanib) is an ATP-competitive inhibitor of RET, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor receptors kinases. In this study, we have studied ZD6474 mechanism of action in TT and MZ-CRC-1 human...
Article
Full-text available
RET/papillary thyroid carcinoma (PTC), TRK-T, or activating mutations of Ras and BRaf are frequent genetic alterations in PTC, all leading to the activation of the extracellular-regulated kinase (Erk) cascade. The aim of this study was to investigate the role of calmodulin-dependent kinase II (CaMKII) in the signal transduction leading to Erk activ...
Article
BRAF gene mutations have been associated with human cancers. Among the naturally occurring mutations, two that involve amino acids of the conserved DFG motif in the activation loop (D594V and G596R), appear to be inactivating. Aim of this study was to analyze the molecular mechanisms involved in the loss of function of B-Raf inactivating mutation G...
Article
Full-text available
The V600E mutation accounts for the vast majority of thyroid carcinoma-associated BRAF mutations. The aim was to study the effects of the two BRAF V600E ATP-competitive kinase inhibitors, PLX4032 and PLX4720, in thyroid carcinoma cell lines. We examined the activity of PLX4032 and PLX4720 in thyroid carcinoma cell lines harboring BRAF V600E (8505C,...
Article
Full-text available
Medullary thyroid carcinoma (MTC) is a rare tumour arising from neural crest-derived parafollicular C-cells. Metastatic MTC patients are incurable because the cancer does not respond to radiotherapy or chemotherapy. The REarranged during Transfection (RET) proto-oncogene plays a key role in the development of MTC. However, one-half of the sporadic...
Article
Full-text available
RET/papillary thyroid carcinoma (RET/PTC) oncoproteins result from the in-frame fusion of the RET receptor tyrosine kinase domain with protein dimerization motifs encoded by heterologous genes. Here, we show that RET/PTC stimulates the beta-catenin pathway. By stimulating PI3K/AKT and Ras/extracellular signal-regulated kinase (ERK), RET/PTC promote...
Article
Full-text available
XB130 is a recently cloned 130 kDa-adaptor protein and Src kinase substrate, structurally similar to actin-filament-associated protein. Here we show that XB130 is predominantly expressed in the thyroid. Given that XB130 is a thyroid-specific tyrosine kinase substrate, we asked whether it is targeted by RET/PTC, a genetically rearranged, constitutiv...
Article
Full-text available
Mutations in BRAF are rare in the follicular variant of papillary thyroid carcinoma (FV-PTC). We identified and functionally characterized a novel T599I-VKSR(600-603)del BRAF mutation in a FV-PTC patient. We analyzed in vitro the effects of this novel mutation in comparison with other thyroid cancer-associated mutations. Expression vectors for the...
Article
Modulation of cytosolic phospholipase A(2) (PLA(2)) expression levels and production of its metabolites have been reported in several tumor types, indicating involvement of arachidonic acid and its derivatives in tumorigenesis. Following our demonstration that the PLA(2) group IV isoform alpha (PLA(2)IV alpha) controls TSH-independent growth of nor...
Article
Full-text available
Anaplastic thyroid carcinoma (ATC) is a rare thyroid cancer type with an extremely poor prognosis. Despite appropriate treatment, which includes surgery, radiotherapy, and chemotherapy, this cancer is invariably fatal. CXCR4 is the receptor for the stromal cell-derived factor-1 (SDF-1)/CXCL12 chemokine and it is expressed in a variety of solid tumo...
Article
Full-text available
RET/papillary thyroid carcinoma (PTC) oncoproteins result from the in-frame fusion of the RET receptor tyrosine kinase with protein dimerization motifs encoded by heterologous genes. Here, we show that RET/PTC1 activates the Rap1 small GTPase. The activation of Rap1 was dependent on the phosphorylation of RET Tyr(1062). RET/PTC1 recruited a complex...
Article
Full-text available
The phosphoinositides have well-defined roles in the control of cellular functions, including cytoskeleton dynamics, membrane trafficking, and cell signaling. However, the interplay among the phosphoinositides and their diffusible derivatives that originate through phospholipase A2 action (the lysophosphoinositides and glycerophosphoinositols) rema...
Article
Full-text available
Activating mutations of the BRAF gene are the most common genetic alterations in papillary thyroid carcinomas (PTCs) and the T1799A transversion, resulting in BRAFV600E, appeared virtually unique in this cancer type. Here, we report on the identification in a classic PTC of a novel BRAF mutation, namely a 1795GTT insertion, resulting in BRAFV599Ins...
Article
Full-text available
Oncogenic conversion of BRAF occurs in approximately 44% of papillary thyroid carcinomas and 24% of anaplastic thyroid carcinomas. In papillary thyroid carcinomas, this mutation is associated with an unfavorable clinicopathologic outcome. Our aim was to exploit BRAF as a potential therapeutic target for thyroid carcinoma. We used RNA interference t...
Article
Full-text available
RAI, also named ShcC/N-Shc, one of the members of the Shc proteins family, is a substrate of the RET receptor tyrosine kinase. Here, we show that RAI forms a protein complex with both RET/MEN 2 A and RET/PTC oncoproteins. By co-immunoprecipitation, we found that RAI associates with the Grb 2-associated binder 1 (GAB 1) adapter. This association is...
Article
Full-text available
The transmembrane glycoprotein CD44v6 is overexpressed in most papillary thyroid carcinomas (PTC). We previously reported that osteopontin (OPN), a secreted glycoprotein that functions as a ligand for CD44v6, is overexpressed in thyrocytes transformed by the RET/PTC oncogene. In this study we asked whether OPN is overexpressed in human PTC samples,...
Article
Full-text available
In papillary thyroid carcinomas (PTCs), rearrangements of the RET receptor (RET/PTC) and activating mutations in the BRAF or RAS oncogenes are mutually exclusive. Here we show that the 3 proteins function along a linear oncogenic signaling cascade in which RET/PTC induces RAS-dependent BRAF activation and RAS- and BRAF-dependent ERK activation. Ado...
Article
Gain-of-function RET mutations are responsible for multiple endocrine neoplasia syndromes (MEN) 2A and 2B and familial medullary thyroid carcinoma (FMTC), whereas loss-of-function mutations are found in Hirschsprung disease. We report a new RET point mutation [R694Q (CGG-->CAG)], serendipitously found in a 23-yr-old woman with hypothyroidism due to...
Article
Activating germ-line point mutations in the RET receptor are responsible for multiple endocrine neoplasia type 2-associated medullary thyroid carcinoma (MTC), whereas somatic RET rearrangements are prevalent in papillary thyroid carcinomas (PTCs). Some rare kindreds, carrying point mutations in RET, are affected by both cancer types, suggesting tha...
Article
Full-text available
To identify genes involved in the transformation of thyroid follicular cells, we explored, using DNA oligonucleotide microarrays, the transcriptional response of PC Cl3 rat thyroid epithelial cells to the ectopic expression of the RET/PTC oncogenes. We found that RET/PTC was able to induce the expression of CXCR4, the receptor for the chemokine CXC...
Article
Full-text available
RET gene rearrangements, which generate chimeric RET/PTC oncogenes, are early events in the evolution of thyroid papillary carcinomas. Expression of RET/PTC oncogenes promotes neoplastic transformation of cultured thyroid cells and of thyroid glands in transgenic mice. Notwithstanding these oncogenic effects, we have found that the expression of tw...

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Project (1)
Project
XB130 is a novel adaptor protein discovered in my lab. We are working on the intracellular signal transduction of adaptor proteins and their functions in vitro and in vivo.