Cancer
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/30804
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Browsing Cancer by Author "Chaudhary, Panka J."
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Item Clinical significance of Annexin A2 expression in Bladder urothelial carcinoma.(2022) Guo, Christina; Chaudhary, Panka J.Purpose: Bladder urothelial carcinoma (BLCA) is a highly malignant cancer, representing the 8th most common cause of cancer death in the US. The unpredictable disease course of BLCA necessitates an accurate biomarker to guide screening, prognosis, and treatment. Our objective was to investigate AnxA2 expression in tumor tissues of bladder urothelial carcinoma patients to determine AnxA2 association with bladder urothelial cancer and implicate AnxA2 as a potential prognostic marker. Methods: We utilized data from The Cancer Genome Atlas (TCGA) to observe AnxA2 gene expression in BLCA and its association with overall survival. Additionally, we quantified AnxA2 protein expression in tumor tissues of BLCA patients via immunohistochemistry. Results: In our analysis of TCGA data, AnxA2 mRNA expression was significantly higher in BLCA tumor tissues compared to normal bladder tissues. In addition, AnxA2 expression was significantly associated with higher tumor stage and grade as well as non-papillary tumor subtypes. The high expression of AnxA2 in BLCA patients was significantly correlated to decreased survival [hazard ratio (HR), 1.78; 95% confidence interval (CI), 1.3-2.44] as compared to low expression. In addition, we found that AnxA2 was significantly upregulated in tumor tissues of bladder urothelial carcinoma patients compared with adjacent non-cancerous bladder tissues. Conclusion: AnxA2 is overexpressed in BLCA patients, which is related to the advanced clinicopathological variables and adverse prognosis of patients with BLCA.Item Phosphorylated Annexin A2 at Tyrosine 23 Regulates Exosome Release and Biogenesis in Triple Negative Breast Cancer(2022) Desai, Priyanka P.; Tripathi, Amit K.; Donkor, Michael; Thyagarajan, Srikantha; Jones, Harlan; Van Treuren, Timothy; Lampe, Jana B.; Chaudhary, Panka J.; Vishwanatha, JamboorPurpose: Exosomes are highly involved in the progression of diverse diseases. Targeting exosome biogenesis and release is a potential strategy for the treatment of the disease like cancer which urges an improved understanding of the process. During the exosomes biogenesis, invagination of the plasma membranes forms early endosomes which mature into late endosomes and multivesicular bodies. Annexin A2 (AnxA2), a calcium dependent phospholipid binding protein, is one of the cargo proteins which gets uploading into the exosomes and impart aggressive phenotype in triple negative breast cancer (TNBC). The mechanism how AnxA2 uploads the exosomal cargo into the exosomes and releases exosomes in the tumor microenvironment remains to be unidentified. In this study, we have explored the potential mechanism for exosome biogenesis and release to target it in TNBC, which lacks the targeted based therapies. Methods: Plasmids expressing constitutive phosphomimetic (AnxA2-Y23E) and non-phosphomimetic AnxA2 (AnxA2-Y23F) mutant gene were transfected in MDA-MB-231 cells. Exosomes isolated from AnxA2-Y23E and AnxA2-Y23F mutant cells were analyzed for expression of the exosomal cargo proteins and RNAs by Western blot and RT-PCR. The number of exosomes released were analyzed by Nanotrack analysis (NTA). Mutant cells treated with Rapamycin, mTORC1(Mammalian Target of Rapamycin Complex 1) inhibitor, were analyzed for the cargo and exosomal secretion. Mutant cells were injected in nude mice to generate tumors. Serum exosomes were isolated and analyzed for cargo and number of exosome release by NTA. Results: In this study, we found that phosphorylated Annexin A2 at tyrosine 23 increases exosome secretion. It loads proteins like AnxA2, CD9 (Cluster of Differentiation 9), LC3B, and Tsg101(Tumor susceptibility gene 101), and AnxA2 and mTOR mRNA into the exosomes. Moreover, secretion and loading of cargo into the exosomes is regulated by increased phosphorylation of AnxA2 and reduced downstream mTORC1 activity. Conclusions: Phosphorylation of AnxA2 at tyrosine 23 regulates exosome secretion and cargo loading into the exosomes in TNBC.