{"id":415982,"date":"2025-06-17T17:01:00","date_gmt":"2025-06-17T09:01:00","guid":{"rendered":"https:\/\/www.um.edu.mo\/news-and-press-releases\/campus-news\/detail\/61355-2\/"},"modified":"2025-06-20T18:24:56","modified_gmt":"2025-06-20T10:24:56","slug":"61355","status":"publish","type":"post","link":"https:\/\/www.um.edu.mo\/pt-pt\/news-and-press-releases\/campus-news\/detail\/61355\/","title":{"rendered":"Equipa de investiga\u00e7\u00e3o da UM descobre novo m\u00e9todo para inibir o cancro da mama triplo-negativo"},"content":{"rendered":"\n                        \n                        <p>A research team led by&nbsp;Kathy Qian Luo, professor in the Faculty of Health Sciences (FHS) at the\nUniversity of Macau (UM), has unveiled a groundbreaking mechanism driving the\nmalignancy of triple-negative breast cancer (TNBC), opening new avenues for\ntargeted therapies. The study revealed that proprotein convertase\nsubtilisin\/kexin type 9 (PCSK9) promotes TNBC progression by depleting\ncholesterol levels in the plasma membrane, thereby activating oncogenic signalling\npathways. These groundbreaking findings suggest that inhibiting PCSK9 or its\ndownstream effectors could significantly suppress TNBC tumour growth and\nmetastasis. The research has been published in the internationally renowned\njournal <i style=\"font-size: 12pt\">Advanced Science<\/i>.<\/p>\n\n<p>TNBC,\ncharacterised by the absence of estrogen receptor, progesterone receptor, and human\nepidermal growth factor receptor 2 (HER2), is the most aggressive breast cancer\nsubtype with limited treatment options and a high metastatic rate. Although\ncholesterol metabolism has been associated with cancer progression, the role of\nPCSK9, a key regulator of cholesterol homeostasis, in TNBC was unclear prior to\nthis study.<\/p>\n\n<p>The\nteam isolated highly metastatic TNBC cells (4-11) from the lung tumours of mice\nthat had been injected with parental MDA-MB-231 cells. Subsequent RNA\nsequencing analysis revealed a significant upregulation of PCSK9 in the metastatic\ncells. The experiment demonstrated that silencing PCSK9 drastically reduced\ntumour growth and metastasis, while overexpressing PCSK9 enhanced these processes.<\/p>\n\n<p>Mechanistically,\nbinding PCSK9 to the low-density lipoprotein receptor (LDLR) reduces\ncholesterol uptake, leading to cholesterol depletion in the plasma membrane. The\ndepletion of cholesterol disrupts lipid rafts, enabling the activation of epidermal\ngrowth factor receptor (EGFR) and HER3. These receptors then drive the\nSrc\/ERK\/c-Jun signalling cascade, which upregulates cyclin D3 and vimentin to promote\ncell proliferation and metastasis. The team further validated these findings using\ninhibitors and activators that target EGFR\/HER3 and related downstream kinases.\nThis conclusively demonstrated the pivotal role of PCSK9-driven malignancy. Notably,\nthe artificial depletion of membrane cholesterol or LDLR produced similar\npro-metastatic effects, confirming that disruption of lipid rafts is a key trigger\nfor the activation of oncogenic pathways. Analysis of clinical data revealed\nthat TNBC patients with high PCSK9 expression had significantly lower survival\nrates. By combining cellular biochemistry with clinical evidence, the study offers\nnew strategies for precision treatment of TNBC.<\/p>\n\n<p>Prof\nLuo is the corresponding author of the study. FHS PhD graduates Li Tianhong and\nWu Renfei are the first and second authors, respectively. The research was funded\nby the Science and Technology Development Fund (FDCT) of the Macao SAR (File No.:\n0147\/2020\/A3 and 0004\/2021\/AKP), and the Ministry of Education Frontiers\nScience Center for Precision Oncology, University of Macau (File No.:\nSP2021-00001-FSCPO and SP2023-00001-FSCPO). The full version of the research\narticle is available at: <a href=\"https:\/\/doi.org\/10.1002\/advs.202408514\">https:\/\/doi.org\/10.1002\/advs.202408514<\/a>.<\/p>\n\n<table style=\"width: 44.7597%;height: 201px\"> <tbody> <tr style=\"height: 21px\"> <td style=\"height: 21px;width: 100.095%\" colspan=\"2\">Source: Faculty of Health Sciences<\/td> <\/tr> <tr style=\"height: 21px\"> <td style=\"height: 21px;width: 56.3278%;min-width: 120px\"> <\/td> <td style=\"height: 21px;width: 43.7669%\"> <\/td> <\/tr> <tr style=\"height: 21px\"> <td style=\"height: 21px;width: 100.095%\" colspan=\"2\">Media Contact Information:<\/td> <\/tr> <tr style=\"height: 21px\"> <td style=\"height: 12px;width: 100.095%\" colspan=\"2\">Communications Office, University of Macau<\/td> <\/tr> <tr style=\"height: 21px\"> <td style=\"height: 21px;width: 56.3278%;min-width: 120px\"> <\/td> <td style=\"height: 21px;width: 43.7669%\"> <\/td> <\/tr> <tr style=\"height: 21px\"> <td style=\"height: 21px;width: 56.3278%;min-width: 120px\">Albee Lei<\/td> <td style=\"height: 21px;width: 43.7669%\">Tel: (853) 8822 8004<\/td> <\/tr> <tr style=\"height: 21px\"> <td style=\"height: 21px;width: 56.3278%;min-width: 120px\">Bell Leong<\/td> <td style=\"height: 21px;width: 43.7669%\">Tel: (853) 8822 8009<\/td> <\/tr> <tr style=\"height: 21px\"> <td style=\"height: 21px;width: 56.3278%;min-width: 120px\">Email:<\/td> <td style=\"height: 21px;width: 43.7669%\"><a href=\"mailto:prs.media@um.edu.mo\">prs.media@um.edu.mo<\/a><\/td>\n<\/tr>\n<tr style=\"height: 21px\">\n<td style=\"height: 21px;width: 56.3278%;min-width: 120px\"> <\/td> <td style=\"height: 21px;width: 43.7669%\"> <\/td> <\/tr> <tr style=\"height: 21px\"> <td style=\"height: 21px;width: 56.3278%;min-width: 120px\"><\/td><td style=\"height: 21px;width: 43.7669%\"><\/td><\/tr>\n<\/tbody>\n<\/table>\n                        \n                        ","protected":false},"excerpt":{"rendered":"<p>A research team led by&nbsp;Kathy Qian Luo, professor in the Faculty of Health Sciences (FHS) at the University of Macau (UM), has unveiled a groundbreaking mechanism driving the malignancy of&#8230;<\/p>\n","protected":false},"author":1,"featured_media":417476,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[61],"tags":[],"class_list":["post-415982","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-campus-news"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v24.5 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Equipa de investiga\u00e7\u00e3o da UM descobre novo m\u00e9todo para inibir o cancro da mama triplo-negativo | Universidade de Macau<\/title>\n<meta name=\"description\" content=\"Universidade de Macau: Uma universidade abrangente p\u00fablica de n\u00edvel internacional fundada em 1981\" \/>\n<meta name=\"robots\" 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