Obesity is a modifiable risk factor associated\u00a0with increased tumour incidence and aggressiveness. Although obesity-associated changes in adipocyte-derived factors are linked to breast cancer progression, the underlying mechanisms remain incompletely understood. Now, Curtin\u00a0et al. identify an oxylipin, 9S-HODE, that is secreted by lean adipocytes to promote ferroptosis of breast cancer cells, thereby suppressing breast cancer progression.<\/p>\n
To determine the mechanism underlying this phenotype, the authors compared gene expression in breast cancer cells treated with lean versus obese secretome, finding that ferroptosis-related transcripts were enriched in lean conditions. Lean secretome culture increased cancer cell death, which could be rescued through treatment with ferroptosis inhibitors. To determine whether lean adipocytes alter iron homeostasis more generally, they measured protein levels of various iron homeostasis-related genes in the cancer cells. Lean secretome led to elevated intracellular ferrous iron and increased expression of haem oxygenase-1 (HMOX1), a regulator of iron metabolism, and CD71, a regulator of iron import, compared with obese secretome. They then confirmed these findings in vivo, demonstrating that the ferroptosis marker 4-HNE was elevated in tumours from lean mice. Treating these mice with a ferroptosis inhibitor increased E0771 tumour growth and reduced 4-HNE levels, suggesting that lean mammary adipocytes increase ferroptosis in breast cancer cells, reducing the overall tumour burden.<\/p>\n","protected":false},"excerpt":{"rendered":"Obesity is a modifiable risk factor associated\u00a0with increased tumour incidence and aggressiveness. Although obesity-associated changes in adipocyte-derived factors…\n","protected":false},"author":2,"featured_media":656668,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[4730,1239,11639,4731,10218,1437,103,61,60,3576],"class_list":["post-656667","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-biomedicine","tag-breast-cancer","tag-cancer-prevention","tag-cancer-research","tag-cell-death","tag-general","tag-health","tag-ie","tag-ireland","tag-metabolic-syndrome"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/656667","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/comments?post=656667"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/656667\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media\/656668"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media?parent=656667"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/categories?post=656667"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/tags?post=656667"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}