Cancer
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/21618
Browse
Browsing Cancer by Author "Chaudhary, Pankaj"
Now showing 1 - 2 of 2
- Results Per Page
- Sort Options
Item HIGH EXPRESSION OF MIEN1 IN BREAST CANCER CORRELATES WITH POOR SURVIVAL OUTCOME(2019-03-05) Chaudhary, Pankaj; Vishwanatha, Jamboor; Nsiah, Nana YaaPURPOSE: Breast cancer is the second leading cause of cancer-related deaths in women. Metastasis accounts for majority of breast cancer deaths. It remains a major barrier to cancer treatment due to limitations in diagnosis and lack of effective therapy. Understanding the role of underlying molecular mechanisms involved in metastasis could lead to effective therapy to prevent and treat breast cancer. Migration and Invasion Enhancer 1 (MIEN1), is a novel gene abundantly expressed in different tumors compared to normal cells. Our previous studies have shown it plays a critical role in regulating cell migration and invasion to promote metastases. It is located on chromosome 17q12 near the Her 2/neu oncogene. MIEN1 protein is a membrane-anchored signal protein, with important structural motifs such as the Immunoreceptor tyrosine-based activation motif (ITAM), a redox active motif and a prenylation sequence at the carboxyl terminal. Here, we evaluated the expression of MIEN1 in breast cancer patients with clinical outcome. METHODS: We analyzed The Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma (BRCA) database to observe MIEN1 mRNA expression in breast cancer subtypes and its correlation with survival. Also, we assessed MIEN1 expression in a panel of normal and breast cancer cell lines using Western blot. RESULTS: MIEN1 gene expression was significantly increased in different subtypes of breast carcinomas (Invasive ductal carcinoma, Invasive lobular carcinoma, Mixed Ductal and Lobular, and Mucinous) compared to normal tissues. Moreover, MIEN1 is predominantly overexpressed in HER2+ breast cancer patients compared to other subtypes. However, MIEN1 expression in luminal A, luminal B and basal-like subtypes were also high in comparison to normal breast tissues. High expression levels of MIEN1 was associated with reduced overall survival (HR = 1.61; 95% CI = 1.34-1.94, P = 0.0001). Screening of MIEN1 expression in various breast cancer cell lines suggest that expression of MIEN1 is high in majority of them compared to immortalized normal mammary epithelial cell line. CONCLUSION: Our findings confirm that MIEN1 is an important oncogene, and its increased expression in breast cancer contributes towards an aggressive disease with poor survival.Item Phosphorylation of Annexin A2 is Essential for its Association with Exosomes in Triple Negative Breast Cancer(2019-03-05) Chaudhary, Pankaj; Sun, Xiangle; Vishwanatha, Jamboor; Desai, PriyankaIntroduction: Studying triple negative breast cancer (TNBC) is the utmost importance as treatment lacks targeted-based therapies. High expression of exosomal Annexin A2 (AnxA2), a Ca+2-dependent phospholipid binding protein, plays an important role in pre-metastatic niche formation and promoting cancer metastasis in TNBC. Also, N-terminal phosphorylation of AnxA2 at Tyrosine (Tyr) 23 has been implicated in several cancer progression. However, the mechanism through which AnxA2 enters into the exosomes has not been elucidated in TNBC. Methods: Plasmids expressing constitutive phosphomimetic AnxA2 (AnxA2-Y23E) and non-phosphomimetic AnxA2 (AnxA2-Y23F) mutant gene were transfected in MDA-MB-231 cells. Transfected cells were functionally validated for AnxA2 specific functions like migration, invasion and proliferation. Exosomes isolated from AnxA2-Y23E (exo-AnxA2-Y23E) and AnxA2-Y23F (exo-AnxA2-Y23F) mutant cells were analyzed for surface expression of AnxA2. Effect of exosomes containing AnxA2-Y23E and AnxA2-Y23F mutant proteins was analyzed on invasiveness and proliferation in cancer cells. Results: Our results showed that MDA-MB-231 TNBC cells expressing phosphomimetic AnxA2 showed increased migratory, invasive and proliferative capacity compared to cells expressing non-phosphomimetic AnxA2. Exosomes derived from phosphomimetic cells had increased AnxA2 expression at surface compared to exosomes derived from non-phosphomimetic cells. In addition, high surface expression of AnxA2 in exosomes derived from phosphomimetic cells induced invasive and proliferative characteristics in CAL-148 breast adenocarcinoma cells compared to exosomes derived from non-phosphomimetic cells (exo-AnxA2-Y23F). Conclusion: Phosphorylation of AnxA2 at Tyr23 plays an important role in imparting metastatic phenotype to the TNBC cells. In addition, the phosphorylation of AnxA2 at Tyr23 is an important event for its entry into the exosomes that promotes invasion and proliferation in cancer cells.