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      SORBS1 inhibits epithelial to mesenchymal transition (EMT) of breast cancer cells by regulating PI3K/AKT signaling and macrophage phenotypic polarization

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          Abstract

          This study aimed to explore the regulatory role of SORBS1 in macrophage polarization and the PI3K/AKT signaling pathway, as well as analyze its mechanism in epithelial-mesenchymal transition (EMT) of breast cancer cells. We established SORBS1-overexpressing and knockout cell lines and verified the effects of SORBS1 on cell viability, invasion, and migration by phenotyping experiments and assaying the expression of associated proteins. Furthermore, we established a breast cancer cell and macrophage co-culture system to validate the effect of SORBS1 expression on macrophage polarization and killing of breast cancer cells. Bioinformatics analysis showed that SORBS1 was lowly expressed in breast cancer (BRCA) samples and highly expressed in healthy tissues. Decreased SORBS1 expression was associated with poor prognosis, and the PI3K/AKT signaling pathway was the most significantly enriched pathway. In vitro experiments showed that high expression of SORBS1 inhibited the migration of breast cancer cells, as well as the PI3K/AKT signaling pathway, and blocked EMT of these cells. In addition, SORBS1 induced macrophage polarization to the M1-type and enhanced the killing effect on breast cancer cells in the co-culture system. In conclusion, we successfully verified that SORBS1 inhibits the invasion and migration of breast cancer cells, induces macrophage M1-type polarization, and blocks EMT of breast cancer cells, and it may act by regulating the PI3K/AKT signaling pathway.

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          UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses1

          Darshan S. Chandrashekar, Bhuwan Bashel, Sai Balasubramanya … (2017)
          Genomics data from The Cancer Genome Atlas (TCGA) project has led to the comprehensive molecular characterization of multiple cancer types. The large sample numbers in TCGA offer an excellent opportunity to address questions associated with tumo heterogeneity. Exploration of the data by cancer researchers and clinicians is imperative to unearth novel therapeutic/diagnostic biomarkers. Various computational tools have been developed to aid researchers in carrying out specific TCGA data analyses; however there is need for resources to facilitate the study of gene expression variations and survival associations across tumors. Here, we report UALCAN, an easy to use, interactive web-portal to perform to in-depth analyses of TCGA gene expression data. UALCAN uses TCGA level 3 RNA-seq and clinical data from 31 cancer types. The portal's user-friendly features allow to perform: 1) analyze relative expression of a query gene(s) across tumor and normal samples, as well as in various tumor sub-groups based on individual cancer stages, tumor grade, race, body weight or other clinicopathologic features, 2) estimate the effect of gene expression level and clinicopathologic features on patient survival; and 3) identify the top over- and under-expressed (up and down-regulated) genes in individual cancer types. This resource serves as a platform for in silico validation of target genes and for identifying tumor sub-group specific candidate biomarkers. Thus, UALCAN web-portal could be extremely helpful in accelerating cancer research. UALCAN is publicly available at http://ualcan.path.uab.edu.
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            Macrophages as tools and targets in cancer therapy

            Alberto Mantovani, Paola Allavena, Federica Marchesi … (2022)
            Tumour-associated macrophages are an essential component of the tumour microenvironment and have a role in the orchestration of angiogenesis, extracellular matrix remodelling, cancer cell proliferation, metastasis and immunosuppression, as well as in resistance to chemotherapeutic agents and checkpoint blockade immunotherapy. Conversely, when appropriately activated, macrophages can mediate phagocytosis of cancer cells and cytotoxic tumour killing, and engage in effective bidirectional interactions with components of the innate and adaptive immune system. Therefore, they have emerged as therapeutic targets in cancer therapy. Macrophage-targeting strategies include inhibitors of cytokines and chemokines involved in the recruitment and polarization of tumour-promoting myeloid cells as well as activators of their antitumorigenic and immunostimulating functions. Early clinical trials suggest that targeting negative regulators (checkpoints) of myeloid cell function indeed has antitumor potential. Finally, given the continuous recruitment of myelomonocytic cells into tumour tissues, macrophages are candidates for cell therapy with the development of chimeric antigen receptor effector cells. Macrophage-centred therapeutic strategies have the potential to complement, and synergize with, currently available tools in the oncology armamentarium.
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              Current and future burden of breast cancer: Global statistics for 2020 and 2040

              Melina Arnold, Eileen Morgan, Harriet Rumgay … (2022)
              Background Breast cancer is the most commonly diagnosed cancer worldwide, and its burden has been rising over the past decades. In this article, we examine and describe the global burden of breast cancer in 2020 and predictions for the year 2040. Methods Estimates of new female breast cancer cases and deaths in 2020 were abstracted from the GLOBOCAN database. Age-standardized incidence and mortality rates were calculated per 100,000 females by country, world region, and level of human development. Predicted cases and deaths were computed based on global demographic projections for the year 2040. Results Over 2.3 million new cases and 685,000 deaths from breast cancer occurred in 2020. Large geographic variation across countries and world regions exists, with incidence rates ranging from <40 per 100,000 females in some Asian and African countries, to over 80 per 100,000 in Australia/New Zealand, Northern America, and parts of Europe. Smaller geographical variation was observed for mortality; however, transitioning countries continue to carry a disproportionate share of breast cancer deaths relative to transitioned countries. By 2040, the burden from breast cancer is predicted to increase to over 3 million new cases and 1 million deaths every year because of population growth and ageing alone. Conclusion Breast cancer is the most common cancer worldwide and continues to have a large impact on the global number of cancer deaths. Global efforts are needed to counteract its growing burden, especially in transitioning countries where incidence is rising rapidly, and mortality rates remain high. • With over 2.3 million new cases and 685,000 deaths in 2020, breast cancer is the most commonly diagnosed cancer worldwide. • Most cases occur in transitioned countries yet transitioning countries have disproportionate share of breast cancer deaths. • The future burden of breast cancer is predicted to increase to over 3 million new cases and 1 million deaths in 2040.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Aging (Albany NY)
                Journal ID (publisher-id): Aging
                Title: Aging (Albany NY)
                Publisher: Impact Journals
                ISSN (Electronic): 1945-4589
                Publication date Collection: 15 March 2024
                Publication date (Electronic): 06 March 2024
                Volume: 16
                Issue: 5
                Pages: 4789-4810
                Affiliations
                [1 ]Department of Surgical, Hebei Medical University, Shijiazhuang 050011, Hebei, China
                [2 ]Department of Oncology, The First Hospital of Qinhuangdao, Qinhuangdao 066600, Hebei, China
                [3 ]Breast Surgery, The First Hospital of Qinhuangdao, Qinhuangdao 066600, Hebei, China
                [4 ]Department of General Surgery, The First Hospital of Qinhuangdao, Qinhuangdao 066600, Hebei, China
                Author notes
                Correspondence to: Yimin Wang; email: drwangyimin@hebmu.edu.cn
                Article
                Publisher ID: 205632 Publisher ID: 205632
                DOI: 10.18632/aging.205632
                PMC ID: 10968685
                PubMed ID: 38451194
                SO-VID: 2c25a0b3-7b94-4bfc-b862-76b348b18240
                Copyright © Copyright: © 2024 Feng et al.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 11 September 2023
                Date accepted : 23 January 2024
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Cell biology
                Keywords: breast cancer cells,pi3k/akt signaling pathway,macrophage polarization,epithelial mesenchymal transition,sorbs1
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: breast cancer cells, pi3k/akt signaling pathway, macrophage polarization, epithelial mesenchymal transition, sorbs1

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