{"id":10074,"date":"2014-09-08T11:27:53","date_gmt":"2014-09-08T15:27:53","guid":{"rendered":"https:\/\/www.bumc.bu.edu\/ppb\/?p=10074"},"modified":"2014-09-08T13:06:53","modified_gmt":"2014-09-08T17:06:53","slug":"researchers-identify-tumor-suppressor-pathway-that-monitors-chromosome-number","status":"publish","type":"post","link":"https:\/\/www.bumc.bu.edu\/ppb\/2014\/09\/08\/researchers-identify-tumor-suppressor-pathway-that-monitors-chromosome-number\/","title":{"rendered":"Researchers Identify Tumor Suppressor Pathway that Monitors Chromosome Number"},"content":{"rendered":"<p class=\"p1\"><a href=\"\/ppb\/files\/2013\/10\/DSC_0015.jpg\"><img loading=\"lazy\" src=\"\/ppb\/files\/2013\/10\/DSC_0015-150x150.jpg\" alt=\"DSC_0015\" width=\"150\" height=\"150\" class=\"size-thumbnail wp-image-8968 alignleft\" \/><\/a>The Laboratory of Cancer Cell Biology has identified the tumor suppressor\u00a0mechanism that\u00a0prevents the oncogenic growth of cells harboring an abnormal number of chromosomes. The study, published in the journal <i>Cell<\/i>, was led by\u00a0Neil J. Ganem, PhD.<\/p>\n<p class=\"p3\">Tetraploid cells, which are a common byproduct of cell division failure, are genomically unstable and have the capacity to facilitate tumorigenesis. Recent estimates suggest that ~40% of all solid tumors have undergone a transient tetraploid intermediate at some point during their evolution, suggesting that tetraploidy plays significant roles in both the development and\/or progression of human malignancies. Given the potentially oncogenic consequences of tetraploidy, it is not\u00a0surprising that\u00a0tumor suppression mechanisms have\u00a0evolved that\u00a0prevent the proliferation of these cells. However, unlike other common cellular insults that trigger cell cycle arrest, such as DNA damage, the mechanisms governing cell cycle\u00a0arrest in response to tetraploidy have been poorly defined.<\/p>\n<p class=\"p3\">\u00a0To understand the mechanism of growth arrest in tetraploid cells, Dr. Ganem and colleagues combined genome-wide RNAi screening and <i>in vitro<\/i> evolution approaches to comprehensively identify all of the genes required to stall the growth of tetraploid cells. Collectively, these data revealed that the Hippo tumor suppressor pathway is specifically activated in tetraploid cells, both <i>in vitro<\/i> and <i>in vivo<\/i>, and that this is the pathway that prevents tetraploid proliferation. The authors pinpointed that defects in the cytoskeleton of tetraploid\u00a0cells\u00a0represented the initial trigger for Hippo pathway\u00a0activation. Notably, analysis of a broad spectrum of human cancers revealed that near-tetraploid tumors frequently adapt to overcome Hippo signaling, suggesting that inactivation or bypass of this pathway may be a prerequisite for the development of high-ploidy tumors. \u00a0\u201cThis work may help guide the development of new therapies that specifically target tumor cells with abnormal numbers of chromosomes, while sparing the normal healthy cells from which they originated,\u201d explained corresponding author Dr. Ganem, PhD,<b> <\/b>Assistant Professor of Pharmacology &amp; Experimental Therapeutics and Medicine in the Shamim and Ashraf Dahod Breast Cancer Research Laboratories at BUSM.<\/p>\n<p class=\"p1\">The study was highlighted with a preview article in\u00a0<i>Cell<\/i>\u00a0and by the journals\u00a0<i>Science Signaling,\u00a0Cancer Discovery, <\/i>and<i>\u00a0Nature Reviews Cancer.\u00a0<\/i>The article can be read online at: <a href=\"http:\/\/www.cell.com\/cell\/abstract\/S0092-8674(14)00820-4\">http:\/\/www.cell.com\/cell\/abstract\/S0092-8674(14)00820-4<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The Laboratory of Cancer Cell Biology has identified the tumor suppressor\u00a0mechanism that\u00a0prevents the oncogenic growth of cells harboring an abnormal number of chromosomes. The study, published in the journal Cell, was led by\u00a0Neil J. Ganem, PhD. Tetraploid cells, which are a common byproduct of cell division failure, are genomically unstable and have the capacity to [&hellip;]<\/p>\n","protected":false},"author":1135,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/www.bumc.bu.edu\/ppb\/wp-json\/wp\/v2\/posts\/10074"}],"collection":[{"href":"https:\/\/www.bumc.bu.edu\/ppb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bumc.bu.edu\/ppb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/ppb\/wp-json\/wp\/v2\/users\/1135"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/ppb\/wp-json\/wp\/v2\/comments?post=10074"}],"version-history":[{"count":2,"href":"https:\/\/www.bumc.bu.edu\/ppb\/wp-json\/wp\/v2\/posts\/10074\/revisions"}],"predecessor-version":[{"id":10080,"href":"https:\/\/www.bumc.bu.edu\/ppb\/wp-json\/wp\/v2\/posts\/10074\/revisions\/10080"}],"wp:attachment":[{"href":"https:\/\/www.bumc.bu.edu\/ppb\/wp-json\/wp\/v2\/media?parent=10074"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/ppb\/wp-json\/wp\/v2\/categories?post=10074"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/ppb\/wp-json\/wp\/v2\/tags?post=10074"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}