Vidya Nallasura's research while affiliated with University of Chicago and other places

Publications (22)

Article
MET is a receptor tyrosine kinase that plays a critical role in proliferation, angiogenesis, invasion, and metastasis. It has been shown to be dysregulated in a number of malignancies, including non-small cell lung cancer (NSCLC). Despite reports of alterations in MET, and its ligand, HGF, being highly associated with advanced pathological stage an...
Article
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Esophageal cancer incidence is rising and has few treatment options. In studying receptor tyrosine kinases associated with esophageal cancers, we have identified EPHB4 to be robustly over expressed in cell lines and primary tumor tissues. In total, 94 squamous cell carcinoma (SCC), 82 adenocarcinoma, 25 dysplasia, 13 Barrett's esophagus and 25 adja...
Article
Paxillin is a 68 kDa focal adhesion protein that provides multiple docking sites at the plasma membrane for an array of signaling molecules and helps form a structural link between the extracellular matrix and the actin cytoskeleton. It is essential in actin filament assembly and focal adhesion formation. Focal adhesion complexes are the drivers of...
Article
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Recurrent/metastatic head and neck cancer remains a devastating disease with insufficient treatment options. We investigated the MET receptor tyrosine kinase as a novel target for the treatment of head and neck squamous cell carcinoma (HNSCC). MET/phosphorylated MET and HGF expression was analyzed in 121 tissues (HNSCC/normal) by immunohistochemist...
Article
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PAX5 is a nuclear transcription factor required for B cell development, and its expression was evaluated in upper aerodigestive malignancies and pancreatic cancer by immunoblotting. The PAX5 protein expression was relatively strong in small-cell lung cancer (SCLC, 11/12); however, its expression was not detected in non-SCLC (NSCLC, n=13), mesotheli...
Article
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Lung cancer is characterized by abnormal cell growth and invasion, and the actin cytoskeleton plays a major role in these processes. The focal adhesion protein paxillin is a target of a number of oncogenes involved in key signal transduction and important in cell motility and migration. In lung cancer tissues, we have found that paxillin was highly...
Article
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The c-MET receptor can be overexpressed, amplified, or mutated in solid tumours including small cell lung cancer (SCLC). In c-MET-overexpressing SCLC cell line NCI-H69, hepatocyte growth factor (HGF) dramatically induced c-MET phosphorylation at phosphoepitopes pY1230/1234/1235 (catalytic tyrosine kinase), pY1003 (juxtamembrane), and also of paxill...
Article
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The c-Met receptor tyrosine kinase is emerging as a novel target in many solid tumors, including lung cancer. PHA-665752 was identified as a small molecule, ATP competitive inhibitor of the catalytic activity of the c-Met kinase. Here, we show that treatment with PHA665752 reduced NCI-H69 (small cell lung cancer) and NCI-H441 (non-small cell lung c...
Article
Although various mutations of the epidermal growth factor receptor (EGFR) gene, most commonly L858R (exon 21) and short exon 19 deletions, have been identified to confer sensitivity toward EGFR tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, it is not known if there are mutations that may result in differential activities of the two inh...
Article
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A 70-year-old Japanese-American woman who had never smoked was diagnosed with stage IV non-small-cell lung cancer with rib metastases. She had previously been well and she had no family history of malignancy. While receiving treatment with erlotinib, an epidermal growth factor receptor small-molecule inhibitor, she progressed and developed new brai...
Article
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c-Met receptor tyrosine kinase (RTK) has not been extensively studied in malignant pleural mesothelioma (MPM). In this study, c-Met was overexpressed and activated in most of the mesothelioma cell lines tested. Expression in MPM tissues by immunohistochemistry was increased (82%) in MPM in general compared with normal. c-Met was internalized with i...
Article
Full-text available
Non-small cell lung cancer (NSCLC) is a difficult disease to treat. The c-Met receptor is an attractive potential target for novel therapeutic inhibition in human cancers. We provide strong evidence that c-Met is overexpressed, activated, and sometimes mutated in NSCLC cell lines and tumor tissues. Expression of c-Met was found in all (100%) of the...

Citations

... It was previously reported that PAX8 and PAX5 are highly expressed in non-small cell lung cancer (NSCLC) and small cell lung cancer cell lines, respectively [14]; but little is known regarding PAX6 expression and function in lung cancer. In this study, we investigated whether PAX6 regulated cell proliferation of NSCLC. ...
... However, the mechanism of the regulation varies among cancer types [25,26]. As an important member of the EPH family, EPHB4 is usually overexpressed in several tumour types, such as ovarian [27], prostate [28], breast, oesophageal [29] and colon cancer [30]. In contrast, EPHB4 was shown to be a tumour suppressor in intestinal carcinoma [31]. ...
... Secondly, physical modifications in the receptor can also constitutively activate c-MET receptor through somatic mutations. Mutations in the kinase domain involving Y123D and Y1230C are majorly involved in the activation of the receptor in HNSCC [86]. Gain in MET copy number is present in almost 16% of the HNSCC patients and associated with an increased c-MET expression and poorer outcome [87]. ...
... [20][21][22] Promoter region hypermethylation of PAX5 was reported in a set of cancer types that included head and neck squamous cell carcinoma, [23] gastric cancer, [21,22] hepatoma, [24] breast cancer, [25,26] and lung cancer. [27][28][29][30] Kurimoto et al [31] showed that methylation of the PAX5 gene promoter region is correlated with poor survival outcomes and reduced cisplatin sensitivity in ESCC. Nevertheless, the exact role and involvement of PAX5 in ESCC progression are poorly understood. ...
... All cases were retrieved from the pathology archives at Rockford Memorial Hospital and the Swedish American Hospital with institutional approval, in accordance with the Institutional Review Board protocol (351597-11 and 17 August 2018). Immunostaining procedures were conducted as described previously [39]. Appropriate negative controls were prepared by omitting the primary antibody step and substituting it with non-immune rabbit serum. ...
... Building on this mechanism, trials of FAK inhibitors alone [116] and with MEK inhibitor trametinib [117] saw improved median PFS in Merlin-negative tumors versus Merlin-positive tumors. Another tyrosine receptor kinase important in cell proliferation and motility is MET, which is overexpressed in mesothelioma [118,119]. Since MET inhibition via tivantinib along with PI3K inhibition suppressed tumor growth and development [120], there is now a phase I/II trial of tivantinib with frontline chemotherapy for mesothelioma and NSCLC [121]. ...
... Most tyrosine kinase domain mutations (85-90%) had a deletion in exon 19 and substitution of L858R in exon 21. Recent studies have also reported a rare exon 22 mutation (E884K) that may reduce sensitivity to different EGFR inhibitors [72]. Several mutations at the cytoplasmic region cause destabilization of the conformation, upregulation of kinase activity, and irregularly promote downstream signaling pathways by avoiding cell apoptosis [73][74][75]. ...
... The Phase I clinical trial of SGX523 to treat solid tumours (NCT00606879) however was terminated due to unexpected renal toxicity [121]. Moreover, there are other characterised small molecules including SU11274 [122] and PHA665752 [123] which so far have shown promising results in in vitro and in vivo studies. ...
... M-CSF) and HGF (Fig. 5C), consistent with our RNA-seq analysis (Fig. 3B). HGF upregulation has also been shown to activate focal adhesion pathway [57,58], consistently, our gene set enrichment analysis (GSEA) using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that genes expressed in TAb2 tumors were enriched in the focal adhesion pathway (Fig. S6A). Gene concept network depicted the genes involved in the enriched pathways in TAb2 tumors (Fig. S6B). ...
... We postulated that a peptide encoding these LD motifs, but lacking FA targeting sequences (LIM domains), would interfere with interactions responsible for FAK FA targeting. We also took into account the fact that several cancer-linked Paxillin mutations have been mapped to the intrinsically disordered regions between LDs and not on the motifs themselves, such as P30S, G105A and A127T that lie between LD1 and LD2 and P233L and T255I that lie between LD3 and LD4 [44,45]. Given the significance of this intermediate linking region, in LD interactions with binding partners and in LD scaffolding functions, we decided that it should be included in the construct [46]. ...