Lysosomes in the mammary gland : their role in mediating cell death

乳腺中的溶酶体：它们在介导细胞死亡中的作用

• 批准号: MR/J001023/1
• 负责人: Christine Watson
• 金额: $ 154.79万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ001023%2F1
• 关键词: Lysosomes; mammary; gland; their; role

Lysosomes are small membrane-bound vesicles, called organelles, that contain a number of enzymes that breakdown large molecules such as DNA and proteins in addition to other organelles such as mitochondria, the so-called powerhouse of the cell. Lysosomes also help to destroy bacteria and viruses that invade cells by digesting them after they have been delivered to the lysosome. Lysosomes are essentially recycling centres as they breakdown old and damaged components and recycle small molecules back to the cell cytoplasm where they are used to rebuild DNA, proteins and organelles. There are a number of debilitating inherited diseases that arise from defects in lysosome function and more recently, lysosomes have been associated with neurodegenerative diseases such as Alzheimer's and also with cancer. We have shown that lysosomes leak their contents during post-lactational regression of the breast and that this causes the death of the breast cells. This new discovery has important implications for breast cancer and other diseases where lysosome function is important. The aim of this project is to investigate how lysosomes become leaky and how this is controlled. We will use a range of techniques including innovative ways to identify novel proteins and measure their localisation in the cell using fluorescence and time-lapse microscopy. We will also investigate any role that these proteins may have in damaging lysosomes and causing them to leak their toxic contents into the cell. We hope that this work will provide new ideas for killing breast cancer cells, that are often resistant to other types of cell death.

溶酶体是一种小的膜结合囊泡，称为细胞器，其中包含许多酶，这些酶可以分解大分子，如DNA和蛋白质，以及其他细胞器，如线粒体，所谓的细胞动力源。在侵入细胞的细菌和病毒被送到溶酶体后，溶酶体也通过消化它们来帮助消灭它们。溶酶体本质上是回收中心，因为它们分解旧的和受损的成分，并将小分子回收到细胞质中，在那里它们被用来重建DNA，蛋白质和细胞器。有许多使人衰弱的遗传性疾病是由溶酶体功能缺陷引起的，最近，溶酶体与神经退行性疾病，如阿尔茨海默氏症和癌症有关。我们已经表明，溶酶体漏出其内容物在哺乳期后乳房退化，这导致乳房细胞的死亡。这一新发现对乳腺癌和其他溶酶体功能重要的疾病具有重要意义。这个项目的目的是研究溶酶体是如何泄漏的，以及如何控制。我们将使用一系列技术，包括创新的方法来识别新的蛋白质，并使用荧光和延时显微镜测量它们在细胞中的定位。我们还将研究这些蛋白质在破坏溶酶体并导致它们将有毒物质泄漏到细胞中的任何作用。我们希望这项工作将为杀死乳腺癌细胞提供新的思路，乳腺癌细胞通常对其他类型的细胞死亡具有抵抗力。

项目成果

Milk makes lysosomes lethal.

牛奶使溶酶体致命。

• DOI: 10.1038/ncb3059
• 发表时间: 2014
• 期刊: Nature cell biology
• 影响因子: 21.3
• 作者: Krishna S

Sinus-like dilatations of the mammary milk ducts, Ki67 expression, and CD3-positive T lymphocyte infiltration, in the mammary gland of wild European rabbits during pregnancy and lactation.

• DOI: 10.1111/joa.12824
• 发表时间: 2018-08
• 期刊: Journal of anatomy
• 影响因子: 2.4
• 作者: Hughes K;Watson CJ
• 通讯作者: Watson CJ

The Mammary Microenvironment in Mastitis in Humans, Dairy Ruminants, Rabbits and Rodents: A One Health Focus.

• DOI: 10.1007/s10911-018-9395-1
• 发表时间: 2018-06
• 期刊: Journal of mammary gland biology and neoplasia
• 影响因子: 2.5
• 作者: Hughes K;Watson CJ
• 通讯作者: Watson CJ

The Multifaceted Role of STAT3 in Mammary Gland Involution and Breast Cancer.

• DOI: 10.3390/ijms19061695
• 发表时间: 2018-06-07
• 期刊: International journal of molecular sciences
• 影响因子: 5.6
• 作者: Hughes K;Watson CJ
• 通讯作者: Watson CJ

Single-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny.

• DOI: 10.1038/ncomms13053
• 发表时间: 2016-10-25
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Davis, Felicity M.;Lloyd-Lewis, Bethan;Harris, Olivia B.;Kozar, Sarah;Winton, Douglas J.;Muresan, Leila;Watson, Christine J.
• 通讯作者: Watson, Christine J.