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      ANXA6: a key molecular player in cancer progression and drug resistance

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          Abstract

          Annexin-A6 (ANXA6), a Ca 2+-dependent membrane binding protein, is the largest of all conserved annexin families and highly expressed in the plasma membrane and endosomal compartments. As a multifunctional scaffold protein, ANXA6 can interact with phospholipid membranes and various signaling proteins. These properties enable ANXA6 to participate in signal transduction, cholesterol homeostasis, intracellular/extracellular membrane transport, and repair of membrane domains, etc. Many studies have demonstrated that the expression of ANXA6 is consistently altered during tumor formation and progression. ANXA6 is currently known to mediate different patterns of tumor progression in different cancer types through multiple cancer-type specific mechanisms. ANXA6 is a potentially valuable marker in the diagnosis, progression, and treatment strategy of various cancers. This review mainly summarizes recent findings on the mechanism of tumor formation, development, and drug resistance of ANXA6. The contents reviewed herein may expand researchers’ understanding of ANXA6 and contribute to developing ANXA6-based diagnostic and therapeutic strategies.

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          Metabolic reprogramming and cancer progression

          Metabolic reprogramming is a hallmark of malignancy. As our understanding of the complexity of tumor biology increases, so does our appreciation of the complexity of tumor metabolism. Metabolic heterogeneity among human tumors poses a challenge to developing therapies that exploit metabolic vulnerabilities. Recent work also demonstrates that the metabolic properties and preferences of a tumor change during cancer progression. This produces distinct sets of vulnerabilities between primary tumors and metastatic cancer, even in the same patient or experimental model. We review emerging concepts about metabolic reprogramming in cancer, with particular attention on why metabolic properties evolve during cancer progression and how this information might be used to develop better therapeutic strategies.
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            Cholesterol metabolism in cancer: mechanisms and therapeutic opportunities

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              Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models

              Cytotoxic chemotherapy is an effective treatment for invasive breast cancer. However, experimental studies in mice also suggest that chemotherapy has pro-metastatic effects. Primary tumours release extracellular vesicles (EVs), including exosomes, that can facilitate the seeding and growth of metastatic cancer cells in distant organs, but the effects of chemotherapy on tumour-derived EVs remain unclear. Here we show that two classes of cytotoxic drugs broadly employed in pre-operative (neoadjuvant) breast cancer therapy, taxanes and anthracyclines, elicit tumour-derived EVs with enhanced pro-metastatic capacity. Chemotherapy-elicited EVs are enriched in annexin A6 (ANXA6), a Ca2+-dependent protein that promotes NF-κB-dependent endothelial cell activation, Ccl2 induction and Ly6C+CCR2+ monocyte expansion in the pulmonary pre-metastatic niche to facilitate the establishment of lung metastasis. Genetic inactivation of Anxa6 in cancer cells or Ccr2 in host cells blunts the pro-metastatic effects of chemotherapy-elicited EVs. ANXA6 is detected, and potentially enriched, in the circulating EVs of breast cancer patients undergoing neoadjuvant chemotherapy.
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                Author and article information

                Contributors
                caojl18@lzu.edu.cn
                ws17352120441@163.com
                1432996042@qq.com
                ery_yangli@lzu.edu.cn
                Journal
                Discov Oncol
                Discov Oncol
                Discover. Oncology
                Springer US (New York )
                2730-6011
                2 May 2023
                2 May 2023
                December 2023
                : 14
                : 53
                Affiliations
                [1 ]GRID grid.411294.b, ISNI 0000 0004 1798 9345, Department of Urology, , Lanzhou University Second Hospital, ; Lanzhou, 730000 China
                [2 ]Gansu Province Clinical Research Center for Urology, Lanzhou, 730000 China
                Article
                662
                10.1007/s12672-023-00662-x
                10154440
                37129645
                d3a743fa-6116-4831-b897-01df3854e9ca
                © The Author(s) 2023

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 February 2023
                : 17 April 2023
                Funding
                Funded by: the Gansu Provincial Education Department outstanding graduate “innovation star” project
                Award ID: 2021CXZX-154
                Award Recipient :
                Funded by: the Open Foundation of Gansu Key Laboratory of Functional Genomics and Molecular Diagnostics
                Funded by: the Second Hospital of Lanzhou University "Cuiying Science and Technology Innovation" project
                Award ID: CY2021-QN-A20
                Award Recipient :
                Funded by: Gansu Province Intellectual Property Planning project
                Award ID: 21ZSCQ012
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2023

                anxa6,migration,drug resistance,metabolic reprogramming,membrane repair

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