Cell Death Discovery最新文献_第6页

Targeting oncogenic MAGEA6 sensitizes triple negative breast cancer to doxorubicin through its autophagy and ferroptosis by stabling AMPKα1. 以致癌物质 MAGEA6 为靶标，通过稳定 AMPKα1 使其自噬和铁变态反应，从而使三阴性乳腺癌对多柔比星敏感。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-06 DOI: 10.1038/s41420-024-02196-9

Hui Zhu, Cheng-Wei Jiang, Wen-Long Zhang, Zhao-Ying Yang, Guang Sun

{"title":"Targeting oncogenic MAGEA6 sensitizes triple negative breast cancer to doxorubicin through its autophagy and ferroptosis by stabling AMPKα1.","authors":"Hui Zhu, Cheng-Wei Jiang, Wen-Long Zhang, Zhao-Ying Yang, Guang Sun","doi":"10.1038/s41420-024-02196-9","DOIUrl":"10.1038/s41420-024-02196-9","url":null,"abstract":"Melanoma-associated antigen A6 (MAGEA6) is well known to have oncogenic activity, but the underlying mechanisms by which it regulates tumor progression and chemo-resistance, especially in triple-negative breast cancer (TNBC), have been unknown. In the study, the differential expression genes (DEGs) in TNBC tumor tissues and TNBC-resistant tumor tissues were analyzed based on TCGA and GEO datasets. MAGEA6, as the most significantly expressed gene, was analyzed by RT-qPCR, western blotting and immunohistochemistry assay in TNBC cell lines and tumor tissues. The potential mechanisms that influence chemo-resistance were also evaluated. Results displayed that MAGEA6 was highly expressed in TNBC and involved in drug resistance. MAGEA6 silencing enhanced the chemo-sensitivity of TNBC to doxorubicin (DOX) in vitro and in vivo, as determined by decreasing IC50 value, proliferation and invasion capacity, and triggering apoptosis. Mechanistically, it was shown that MAGEA6 depletion sensitized TNBC to DOX via regulating autophagy. Ubiquitination assay displayed that knockdown of MAGEA6 decreased the AMPKα1 ubiquitination, thereby elevating the levels of AMPKα1 and p-AMPKα in TNBC cells. Importantly, AMPK inhibitor (Compound C) can reduce the LC3II/I level induced by sh-MAGEA6, indicating that sh-MAGEA6 activated AMPK signaling through suppressing AMPKα1 ubiquitination and then facilitated autophagy in TNBC. Furthermore, we also observed that AMPK is required for SLC7A11 to regulate ferroptosis, and supported the crux roles of MAGEA6/AMPK/SLC7A11-mediated ferroptosis on modulating DOX sensitivity in TNBC cells. These findings indicated that targeting MAGEA6 can enhance the chemo-sensitivity in TNBC via activation of autophagy and ferroptosis; its mechanism involves AMPKα1-dependent autophagy and AMPKα1/SLC7A11-induced ferroptosis.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"430"},"PeriodicalIF":6.1,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nuclear PCGF3 inhibits the antiviral immune response by suppressing the interferon-stimulated gene. 核 PCGF3 通过抑制干扰素刺激基因来抑制抗病毒免疫反应。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-05 DOI: 10.1038/s41420-024-02194-x

Gula Da, Junmin Wang, Jing Shang, Cuiping Xun, Yang Yu, Yong Wang, Ning Tie, Hongbin Li

{"title":"Nuclear PCGF3 inhibits the antiviral immune response by suppressing the interferon-stimulated gene.","authors":"Gula Da, Junmin Wang, Jing Shang, Cuiping Xun, Yang Yu, Yong Wang, Ning Tie, Hongbin Li","doi":"10.1038/s41420-024-02194-x","DOIUrl":"10.1038/s41420-024-02194-x","url":null,"abstract":"Type I interferon (IFN-I) plays a crucial role in the antiviral immune response and inflammatory autoimmune diseases by inducing the expression of IFN-stimulated genes (ISGs). Hence, the regulation of ISG expression is fundamental for maintaining immune homeostasis. In this study, we found that PCGF3 negatively regulates the antiviral response by suppressing the expression of ISGs. The deficiency of PCGF3 in innate immune cells results in an augmented expression of ISGs in response to IFN-I stimulation. Mechanistically, PCGF3 is recruited to interferon-stimulated response elements (ISREs) region in an IFN-dependent way, precluding STAT1 from binding to the ISG promoter and diminishing ISRE activity. Additionally, we observed a negative correlation between decreased PCGF3 expression and elevated ISG expression in peripheral blood mononuclear cells (PBMCs) of patients with dermatomyositis (DM). Our findings clarified the epigenetic regulatory role of PCGF3 in inhibiting the excessive expression of ISGs induced by IFN-I under pathological circumstances.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"429"},"PeriodicalIF":6.1,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11455894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulation of HNRNP family by post-translational modifications in cancer. 癌症中翻译后修饰对 HNRNP 家族的调控。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-04 DOI: 10.1038/s41420-024-02198-7

Bohao Li, Mingxin Wen, Fei Gao, Yunshan Wang, Guangwei Wei, Yangmiao Duan

{"title":"Regulation of HNRNP family by post-translational modifications in cancer.","authors":"Bohao Li, Mingxin Wen, Fei Gao, Yunshan Wang, Guangwei Wei, Yangmiao Duan","doi":"10.1038/s41420-024-02198-7","DOIUrl":"10.1038/s41420-024-02198-7","url":null,"abstract":"Heterogeneous nuclear ribonucleoproteins (HNRNPs) represent a large family of RNA-binding proteins consisting of more than 20 members and have attracted great attention with their distinctive roles in cancer progression by regulating RNA splicing, transcription, and translation. Nevertheless, the cancer-specific modulation of HNRNPs has not been fully elucidated. The research of LC-MS/MS technology has documented that HNRNPs were widely and significantly targeted by different post-translational modifications (PTMs), which have emerged as core regulators in shaping protein functions and are involved in multiple physiological processes. Accumulating studies have highlighted that several PTMs are involved in the mechanisms of HNRNPs regulation in cancer and may be suitable therapeutic targets. In this review, we summarize the existing evidence describing how PTMs modulate HNRNPs functions on gene regulation and the involvement of their dysregulation in cancer, which will help shed insights on their clinical impacts as well as possible therapeutic tools targeting PTMs on HNRNPs.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"427"},"PeriodicalIF":6.1,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

4-aminopyridine attenuates inflammation and apoptosis and increases angiogenesis to promote skin regeneration following a burn injury in mice. 4- 氨基吡啶可减轻炎症和细胞凋亡，增加血管生成，从而促进小鼠烧伤后的皮肤再生。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-04 DOI: 10.1038/s41420-024-02199-6

Rahul V G, Govindaraj Ellur, Amir A Gaber, Prem Kumar Govindappa, John C Elfar

{"title":"4-aminopyridine attenuates inflammation and apoptosis and increases angiogenesis to promote skin regeneration following a burn injury in mice.","authors":"Rahul V G, Govindaraj Ellur, Amir A Gaber, Prem Kumar Govindappa, John C Elfar","doi":"10.1038/s41420-024-02199-6","DOIUrl":"10.1038/s41420-024-02199-6","url":null,"abstract":"Severe thermal skin burns are complicated by inflammation and apoptosis, which delays wound healing and contributes to significant morbidity. Diverse treatments demonstrate limited success in mitigating these processes to accelerate healing. Agents that alter cell behavior to improve healing would alter treatment paradigms. We repurposed 4-aminopyridine (4-AP), a drug approved by the US FDA for multiple sclerosis, to treat severe burns in mice (10-week-old C57BL/6 J male mice weighing 25 ± 3 g). We found that 4-AP, in the early stages of burn healing, significantly reduced the expression of pro-inflammatory cytokines IL1β and TNFα while increasing the expression of anti-inflammatory markers CD206, ARG-1, and IL10. We demonstrated increased intracellular calcium effects of 4-AP through Orai1-pSTAT6 signaling, where 4-AP significantly mitigated inflammatory effects by promoting M2 macrophage differentiation in in-vitro macrophages and post-skin burn tissues. 4-AP attenuated apoptosis, with decreases in apoptotic markers BAX, caspase-9, and caspase-3 and increases in anti-apoptotic markers BCL2 and BCL-XL. Furthermore, 4-AP promoted angiogenesis through increases in the expression of CD31, VEGF, and eNOS. Together, these likely contributed to accelerated burn wound closure, as demonstrated in increased keratinocyte proliferation (K14) and differentiation (K10) markers. In the later stages of burn healing, 4-AP increased TGFβ and FGF levels, which are known to mark the transformation of fibroblasts to myofibroblasts. This was further demonstrated by an increased expression of α-SMA and vimentin, as well as higher levels of collagen I and III, MMP 3, and 9 in mice treated with 4-AP. Our findings support the idea that 4-AP may have a novel, clinically relevant therapeutic use in promoting burn wound healing.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"428"},"PeriodicalIF":6.1,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CircGSK3β mediates PD-L1 transcription through miR-338-3p/PRMT5/H3K4me3 to promote breast cancer cell immune evasion and tumor progression. CircGSK3β 通过 miR-338-3p/PRMT5/H3K4me3 介导 PD-L1 转录，促进乳腺癌细胞免疫逃避和肿瘤进展。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-04 DOI: 10.1038/s41420-024-02197-8

Lin Liang, Mengxiang Gao, Wentao Li, Jingqiong Tang, Qian He, Feng Zeng, Jiaying Cao, Siyi Liu, Yan Chen, Xin Li, Yanhong Zhou

{"title":"CircGSK3β mediates PD-L1 transcription through miR-338-3p/PRMT5/H3K4me3 to promote breast cancer cell immune evasion and tumor progression.","authors":"Lin Liang, Mengxiang Gao, Wentao Li, Jingqiong Tang, Qian He, Feng Zeng, Jiaying Cao, Siyi Liu, Yan Chen, Xin Li, Yanhong Zhou","doi":"10.1038/s41420-024-02197-8","DOIUrl":"10.1038/s41420-024-02197-8","url":null,"abstract":"Circular RNA (circRNA) plays a pivotal role in breast cancer onset and progression. Understanding the biological functions and underlying molecular mechanisms of dysregulated circRNAs in breast cancer is crucial for elucidating its pathogenesis and identifying potential therapeutic targets. In this study, we investigated the role and molecular mechanism of circGSK3β in breast cancer. We found that circGSK3β is highly expressed in breast cancer cell lines, where it promotes cell proliferation, migration, and invasion, thereby driving breast cancer progression. Furthermore, we observed a close association between circGSK3β expression levels and immune evasion in breast cancer cells. Mechanistically, circGSK3β acts as a competing endogenous RNA (ceRNA) by interacting with miR-338-3p, thereby promoting breast cancer cell proliferation, migration, and invasion. Additionally, circGSK3β positively regulates the expression of the target gene PRMT5 through its interaction with miR-338-3p. This, in turn, enhances H3K4me3 recruitment to the promoter region of PD-L1, resulting in upregulation of PD-L1 expression and consequent immune evasion in breast cancer. In summary, our findings underscore the significance of the circGSK3β-miR-338-3p-PRMT5-H3K4me3 axis in promoting breast cancer progression and immune evasion. CircGSK3β emerges as a critical player in breast cancer pathogenesis, potentially serving as a diagnostic and prognostic marker, and offering novel insights into the role of circRNAs in breast cancer progression.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"426"},"PeriodicalIF":6.1,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TRIB3 inhibition by palbociclib sensitizes prostate cancer to ferroptosis via downregulating SOX2/SLC7A11 expression. 帕博西尼（palbociclib）抑制TRIB3可通过下调SOX2/SLC7A11的表达，使前列腺癌对铁变态反应敏感。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-03 DOI: 10.1038/s41420-024-02152-7

Yangyi Zhang, Chenyu Liu, Yalan Yang, He Ren, Tianyi Ren, Yinuo Huang, Shinan Zhang, Qiang Sun, Hongyan Huang

{"title":"TRIB3 inhibition by palbociclib sensitizes prostate cancer to ferroptosis via downregulating SOX2/SLC7A11 expression.","authors":"Yangyi Zhang, Chenyu Liu, Yalan Yang, He Ren, Tianyi Ren, Yinuo Huang, Shinan Zhang, Qiang Sun, Hongyan Huang","doi":"10.1038/s41420-024-02152-7","DOIUrl":"10.1038/s41420-024-02152-7","url":null,"abstract":"Palbociclib is a CDK4/6 inhibitor approved for the treatment of breast cancer by suppressing cell proliferation. However, monotherapy with palbociclib was discouraging in prostate cancer, calling for a mechanism-based effective therapy. In this study, we reported in prostate cancer that palbociclib is a potent sensitizer of ferroptosis, which is worked out by downregulating the expression of TRIB3, a gene highly expressed in prostate cancer. Specifically, TRIB3 knockdown augmented the response of prostate cancer cells to ferroptosis inducers, whereas, TRIB3 overexpression rescued prostate cancer cells from palbociclib-induced ferroptosis. Mechanistically, TRIB3 inhibition by palbociclib resulted in downregulation of SOX2, which subsequently led to compromised expression of SLC7A11, a cystine/glutamate antiporter that counteracts ferroptosis. Functionally, a combined treatment of palbociclib with ferroptosis inducer significantly suppressed prostate cancer growth in a xenograft tumor model. Together, these results uncover an essential role of TRIB3/SOX2/SLC7A11 axis in palbociclib-induced ferroptosis, suggesting palbociclib a promising targeted therapy in combine with ferroptosis induction for the treatment of prostate cancer.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"425"},"PeriodicalIF":6.1,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Repair and regeneration: ferroptosis in the process of remodeling and fibrosis in impaired organs. 修复与再生：受损器官重塑和纤维化过程中的铁蛋白沉积。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-02 DOI: 10.1038/s41420-024-02181-2

Jiali Yin, Xinjun Xu, Ying Guo, Caiyu Sun, Yujuan Yang, Huifang Liu, Pengyi Yu, Tong Wu, Xicheng Song

{"title":"Repair and regeneration: ferroptosis in the process of remodeling and fibrosis in impaired organs.","authors":"Jiali Yin, Xinjun Xu, Ying Guo, Caiyu Sun, Yujuan Yang, Huifang Liu, Pengyi Yu, Tong Wu, Xicheng Song","doi":"10.1038/s41420-024-02181-2","DOIUrl":"10.1038/s41420-024-02181-2","url":null,"abstract":"As common clinical-pathological processes, wound healing and tissue remodelling following injury or stimulation are essential topics in medical research. Promoting the effective healing of prolonged wounds, improving tissue repair and regeneration, and preventing fibrosis are important and challenging issues in clinical practice. Ferroptosis, which is characterized by iron overload and lipid peroxidation, is a nontraditional form of regulated cell death. Emerging evidence indicates that dysregulated metabolic pathways and impaired iron homeostasis play important roles in various healing and regeneration processes via ferroptosis. Thus, we review the intrinsic mechanisms of tissue repair and remodeling via ferroptosis in different organs and systems under various conditions, including the inflammatory response in skin wounds, remodeling of joints and cartilage, and fibrosis in multiple organs. Additionally, we summarize the common underlying mechanisms, key molecules, and targeted drugs for ferroptosis in repair and regeneration. Finally, we discuss the potential of therapeutic agents, small molecules, and novel materials emerging for targeting ferroptosis to promote wound healing and tissue repair and attenuate fibrosis.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"424"},"PeriodicalIF":6.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aberrant activation of a miR-101-UBE2D1 axis contributes to the advanced progression and chemotherapy sensitivity in human hepatocellular carcinoma. miR-101-UBE2D1 轴的异常激活导致人类肝细胞癌的晚期进展和化疗敏感性。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-01 DOI: 10.1038/s41420-024-02193-y

Xiuli Mu, Yuchen Wei, Xin Fan, Rui Zhang, Wenjin Xi, Guoxu Zheng, An-Gang Yang

{"title":"Aberrant activation of a miR-101-UBE2D1 axis contributes to the advanced progression and chemotherapy sensitivity in human hepatocellular carcinoma.","authors":"Xiuli Mu, Yuchen Wei, Xin Fan, Rui Zhang, Wenjin Xi, Guoxu Zheng, An-Gang Yang","doi":"10.1038/s41420-024-02193-y","DOIUrl":"10.1038/s41420-024-02193-y","url":null,"abstract":"Chemotherapeutic drugs, such as cisplatin (cis-dichlorodiamineplatinum [II], cDDP) and 5-fluorouracil (5Fu), are widely used in transarterial chemoembolization (TACE), which is a standard therapy for patients with hepatocellular carcinoma (HCC). Chemoresistance is a major cause of TACE treatment failure in HCC patients. Our previous studies have identified the expression levels of miR-101 responsive genes, such as EED, EZH2, STMN1 and JUNB, exhibit significant correlation with the occurrence and progression of HCC, while the role of miR-101 responsive gene signatures in the chemoresistance of HCC treatment remains unclear. In this study, we identified ubiquitin-coupled enzyme E2D1 (UBE2D1) as a crucial regulatory factor in the chemoresistance of HCC, which is a direct target of miR-101 and exhibits significant correlation with miR-101-responsive gene signatures. The bioinformatics analysis showed the expression of UBE2D1 was significantly increased in HCC tissues and was closely correlated with the poor prognosis. In addition, we analyzed the role of miR-101/UBE2D1 axis in regulating chemo-sensitive of HCC cells. Our results showed that miR-101 increases the DNA damage and apoptosis of HCC cells by inhibiting the expression of UBE2D1, which in turn increases the sensitivity of HCC cells to cDDP and 5Fu both in vitro and in vivo. Therefore, simultaneous assessment of miR-101 and UBE2D1 expression levels might provide an effective approach in preselecting HCC patients with survival benefit from TACE treatment. Moreover, further elucidation of the underlying molecular mechanisms of the miR-101/UBE2D1 axis could provide novel insight for targeted therapy of HCC.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"422"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TMCO1 is upregulated in breast cancer and regulates the response to pro-apoptotic agents in breast cancer cells. TMCO1 在乳腺癌中上调，并调节乳腺癌细胞对促凋亡药物的反应。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-01 DOI: 10.1038/s41420-024-02183-0

Alice H L Bong, Mélanie Robitaille, Sichun Lin, Amy McCart-Reed, Michael Milevskiy, Stéphane Angers, Sarah J Roberts-Thomson, Gregory R Monteith

{"title":"TMCO1 is upregulated in breast cancer and regulates the response to pro-apoptotic agents in breast cancer cells.","authors":"Alice H L Bong, Mélanie Robitaille, Sichun Lin, Amy McCart-Reed, Michael Milevskiy, Stéphane Angers, Sarah J Roberts-Thomson, Gregory R Monteith","doi":"10.1038/s41420-024-02183-0","DOIUrl":"10.1038/s41420-024-02183-0","url":null,"abstract":"The release of Ca2+ ions from endoplasmic reticulum calcium stores is a key event in a variety of cellular processes, including gene transcription, migration and proliferation. This release of Ca2+ often occurs through inositol 1,4,5-triphosphate receptors and the activity of these channels and the levels of stored Ca2+ in the endoplasmic reticulum are important regulators of cell death in cancer cells. A recently identified Ca2+ channel of the endoplasmic reticulum is transmembrane and coiled-coil domains 1 (TMCO1). In this study, we link the overexpression of TMCO1 with prognosis in node-positive basal breast cancer patients. We also identify interacting proteins of TMCO1, which include endoplasmic reticulum-resident proteins involved in Ca2+ regulation and proteins directly involved in nucleocytoplasmic transport. Interacting proteins included nuclear transport proteins and TMCO1 was shown to have both nuclear and endoplasmic reticulum localisation in MDA-MB-231 basal breast cancer cells. These studies also define a role for TMCO1 in the regulation of breast cancer cells in their sensitivity to BCL-2/MCL-1 inhibitors, analogous to the role of inositol 1,4,5-triphosphate receptors in the regulation of cell death pathways activated by these agents.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"421"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the crucial role of ferroptosis in host resistance to streptococcus agalactiae infection. 揭示铁蛋白沉积在宿主抵抗无乳链球菌感染中的关键作用。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-01 DOI: 10.1038/s41420-024-02189-8

Jia-Xuan Yi, Ze-Yu Sun, Peng Liu, Yu-Hang Wang, Hui Liu, Qing-Yu Lv, De-Cong Kong, Wen-Hua Huang, Yu-Hao Ren, Qian Li, Yong-Qiang Jiang, Jing Li, Hua Jiang

{"title":"Unveiling the crucial role of ferroptosis in host resistance to streptococcus agalactiae infection.","authors":"Jia-Xuan Yi, Ze-Yu Sun, Peng Liu, Yu-Hang Wang, Hui Liu, Qing-Yu Lv, De-Cong Kong, Wen-Hua Huang, Yu-Hao Ren, Qian Li, Yong-Qiang Jiang, Jing Li, Hua Jiang","doi":"10.1038/s41420-024-02189-8","DOIUrl":"10.1038/s41420-024-02189-8","url":null,"abstract":"IL-1β represents an important inflammatory factor involved in the host response against GBS infection. Prior research has suggested a potential involvement of IL-1β in the process of ferroptosis. However, the relationship between IL-1β and ferroptosis in the context of anti-GBS infection remains uncertain. This research demonstrates that the occurrence of ferroptosis is essential for the host's defense against GBS infection in a mouse model of abdominal infection, with peritoneal macrophages identified as the primary cells undergoing ferroptosis. Further research indicates that IL-1β induces lipid oxidation in macrophages through the upregulation of pathways related to lipid oxidation. Concurrently, IL-1β is not only involved in the initiation of ferroptosis in macrophages, but its production is intricately linked to the onset of ferroptosis. Ultimately, we posit that ferroptosis acts as a crucial initiating factor in the host response to GBS infection, with IL-1β playing a significant role in the resistance to infection by serving as a key inducer of ferroptosis.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"423"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0