Department Of Human Genetics And Molecular Medicine

Permanent URI for this communityhttps://kr.cup.edu.in/handle/32116/103

Browse

Search Results

Now showing 1 - 4 of 4
  • Item
    High levels of unfolded protein response component CHAC1 associates with cancer progression signatures in malignant breast cancer tissues
    (Springer Science and Business Media Deutschland GmbH, 2022-08-05T00:00:00) Mehta, Vikrant; Suman, Prabhat; Chander, Harish
    Purpose: The aberrant mRNA expression of a UPR component Cation transport regulator homolog 1 (CHAC1) has been reported to be associated with poor survival in breast and ovarian cancer patients, however, the expression of CHAC1 at protein levels in malignant breast tissues is underreported. The following study aimed at analyzing CHAC1 protein expression in malignant breast cancer tissues. Methods: Evaluation of CHAC1 expression in invasive ductal carcinomas (IDCs) with known ER, PR, and HER2 status was carried out using immunohistochemistry (IHC) with CHAC1 specific antibody. The Human breast cancer tissue microarray (TMA, cat# BR1503f, US Biomax, Inc., Rockville, MD) was used to determine CHAC1 expression. The analysis of CHAC1 IHC was done to determine its expression in terms of molecular subtypes of breast cancer, lymph node status, and proliferation index using Qu-Path software. Survival analysis was studied with a Kaplan�Meier plotter. Results: Immunohistochemical analysis of CHAC1 in breast cancer tissues showed significant up-regulation of CHAC1 as compared to the adjacent normal and benign tissues. Interestingly, CHAC1 immunostaining revealed high expression in tumor tissues with high proliferation and positive lymph node metastasis suggesting that CHAC1 might have an important role to play in breast cancer progression. Furthermore, high CHAC1 expression is associated with poor overall survival (OS) in large breast cancer patient cohorts. Conclusion: As a higher expression of CHAC1 was observed in tissue cores with high Ki67 index and positive lymph node metastasis it may be concluded that enhanced CHAC1 expression correlates with proliferation and metastasis. The further analysis of breast cancer patients� survival data through KM plot indicated that high CHAC1 expression is associated with a bad prognosis hinting that CHAC1 may have a possible prognostic significance in breast cancer. � 2022, The Author(s), under exclusive licence to Federaci�n de Sociedades Espa�olas de Oncolog�a (FESEO).
  • Item
    Prognostic significance of CHAC1 expression in breast cancer
    (Springer Science and Business Media B.V., 2022-06-21T00:00:00) Mehta, Vikrant; Meena, Jaipal; Kasana, Harit; Munshi, Anjana; Chander, Harish
    Background: An emerging component of Unfolded Protein Response (UPR) pathway, cation transport regulator homolog 1 (CHAC1) has been conferred with the ability to degrade intracellular glutathione and induce apoptosis, however, many reports have suggested a role of CHAC1 in cancer progression. Our study aimed to investigate CHAC1 mRNA levels in large breast cancer datasets using online tools and both mRNA and protein levels in different breast cancer cell lines. Methods and results: Analysis of clinical information from various online tools (UALCAN, GEPIA2, TIMER2, GENT2, UCSCXena, bcGenExMiner 4.8, Km Plotter, and Enrichr) was done to elucidate the CHAC1 mRNA expression in large breast cancer patient dataset and its correlation with disease progression. Later, in vitro techniques were employed to explore the mRNA and protein expression of CHAC1 in breast cancer cell lines. Evidence from bioinformatics analysis as well as in vitro studies indicated a high overall expression of CHAC1 in breast tumor samples and had a significant impact on the prognosis and survival of patients. Enhanced CHAC1 levels in the aggressive breast tumor subtypes such as Human Epidermal growth factor receptor 2 (HER2) and Triple Negative Breast Cancer (TNBC) were evident. Our findings hint toward the possible role of CHAC1 in facilitating the aggressiveness of breast cancer and the disease outcome. Conclusion: In summary, CHAC1 is constantly up-regulated in breast cancer leading to a poor prognosis. CHAC1, therefore, could be a promising candidate in the analysis of breast cancer diagnosis and prognosis. � 2022, The Author(s), under exclusive licence to Springer Nature B.V.
  • Thumbnail Image
    Item
    KIBRA Team Up with Partners to Promote Breast Cancer Metastasis
    (Springer, 2019) Singh G; Mishra, S; Chander, Harish
    Among women, breast cancer is the most frequently diagnosed cancer. Most of the breast cancers represent metastasis to distant organs at the time of diagnosis and accounts for the majority of deaths. Metastasis is characterized by many genetic aberrations including mutations, overexpression of oncogenes etc. KIBRA (KIdney/BRAin protein), a scaffolding protein is recently described as an important player in the process of invasion and metastasis. The Kidney/BRAin protein through its different domains interacts with various proteins to couple cytoskeleton arrangement, cell polarity and migration. N terminal and C terminal of the protein contains the WW, Internal C 2 & putative class III PDZ domain that interacts with DDR1, DLC1 & PKCζ. These protein-protein interactions equip the breast cancer cells to invade and metastasize. Here, we discuss a comprehensive knowledge about the KIBRA protein, its domains and the interacting partners involved in metastasis of breast cancer. © 2019, Arányi Lajos Foundation.
  • Item
    CIP4 promotes metastasis in triple-negative breast cancer and is associated with poor patient prognosis
    (Impact Journals, 2015) Cerqueira, Otto L.D.; Truesdell, Peter; Baldassarre, Tomas; Vilella-Arias, Santiago A.; Watt, Kathleen; Meens, Jalna; Chander, Harish; Os-rio, Cynthia A.B.; Soares, Fernando A.; Reis, Eduardo M.; Craig, Andrew W.B.
    Signaling via epidermal growth factor receptor (EGFR) and Src kinase pathways promote triple-negative breast cancer (TNBC) cell invasion and tumor metastasis. Here, we address the role of Cdc42-interacting protein-4 (CIP4) in TNBC metastasis in vivo, and profile CIP4 expression in human breast cancer patients. In human TNBC cells, CIP4 knock-down (KD) led to less sustained activation of Erk kinase and impaired cell motility compared to control cells. This correlated with significant defects in 3D invasion of surrounding extracellular matrix by CIP4 KD TNBC cells when grown as spheroid colonies. In mammary orthotopic xenograft assays using both human TNBC cells (MDA-MB-231, HCC 1806) and rat MTLn3 cells, CIP4 silencing had no overt effect on tumor growth, but significantly reduced the incidence of lung metastases in each tumor model. In human invasive breast cancers, high CIP4 levels was significantly associated with high tumor stage, TNBC and HER2 subtypes, and risk of progression to metastatic disease. Together, these results implicate CIP4 in promoting metastasis in TNBCs.