{"id":3933,"date":"2019-07-27T16:13:38","date_gmt":"2019-07-27T07:13:38","guid":{"rendered":"http:\/\/163.180.4.222\/lab\/?p=3933"},"modified":"2019-07-27T16:13:38","modified_gmt":"2019-07-27T07:13:38","slug":"flower-power-as-human-cancer-cells-compete-with-normal-cells","status":"publish","type":"post","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=3933","title":{"rendered":"Flower power as human cancer cells compete with normal cells"},"content":{"rendered":"<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<h5>Cells compete for survival during development. It emerges that mammalian cells on a path to form a tumour express specific versions of the protein Flower when they vie for survival with surrounding normal cells.<\/h5>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<div class=\"article__body serif cleared\">\n<p>In multicellular organisms, cells usually communicate with each other in a peaceful manner. But harmony is shattered if abnormal cells appear and battle for space and survival with normal cells in a process called cell competition. This process was identified in the fruit fly\u00a0<i>Drosophila<\/i><i>melanogaster<\/i><sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-02161-y?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR1\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">1<\/a><\/sup>, and it also occurs in mammals<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-02161-y?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR2\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">2<\/a><\/sup>. When cancer starts to form in mammals, competition occurs between normal cells and those on a path to tumour formation, but how the molecular differences between such cells trigger cell competition is poorly understood.\u00a0<a href=\"https:\/\/www.nature.com\/articles\/s41586-019-1429-3\" data-track=\"click\" data-label=\"https:\/\/www.nature.com\/articles\/s41586-019-1429-3\" data-track-category=\"body text link\">Writing in\u00a0<i>Nature<\/i><\/a>, Madan\u00a0<i>et al.<\/i><sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-02161-y?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR3\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">3<\/a><\/sup>\u00a0report that whether competing mammalian cells win such a battle depends on which version of a membrane protein called Flower they express.<\/p>\n<p>&nbsp;<\/p>\n<aside class=\"recommended pull pull--left sans-serif\" data-label=\"Related\"><a href=\"https:\/\/www.nature.com\/articles\/s41586-019-1429-3\" data-track=\"click\" data-track-label=\"recommended article\"><img decoding=\"async\" class=\"recommended__image\" src=\"https:\/\/media.nature.com\/w400\/magazine-assets\/d41586-019-02161-y\/d41586-019-02161-y_16971614.jpg\" \/><\/a><\/p>\n<p class=\"recommended__title serif\">Read the paper: Flower isoforms promote competitive growth in cancer<\/p>\n<\/aside>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>Earlier work<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-02161-y?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR4\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">4<\/a><\/sup>\u00a0in\u00a0<i>D. melanogaster\u00a0<\/i>revealed that, during cell competition, the cells that survive (winner cells) are distinguished from the cells that die (loser cells) by the version of Flower protein (FWE) that they express. Different versions of this protein are made when the messenger RNA that encodes FWE undergoes a process called alternative splicing. Loser cells express a version of FWE termed FWE<sup>Lose<\/sup>\u00a0and winner cells express a version termed FWE<sup>Win<\/sup>. When loser cells come into contact with winner cells, the former cells die and the latter divide to fill the empty space left by this cell death<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-02161-y?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR4\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">4<\/a><\/sup>. An encounter between cells that express FWE<sup>Lose<\/sup>\u00a0and those that express FWE<sup>Win<\/sup>\u00a0is required for cell death to occur because cells that express FWE<sup>Lose<\/sup>\u00a0survive if cells expressing FWE<sup>Win<\/sup>\u00a0are absent<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-02161-y?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR4\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">4<\/a><\/sup>. However, whether a comparable FWE system functions in mammals was unknown.<\/p>\n<p>Madan and colleagues report that alternative splicing generates four versions of human FWE, which they term FWE1, FWE2, FWE3 and FWE4. Using human breast cancer cells grown\u00a0<i>in vitro<\/i>, the authors examined whether any of these versions of FWE behave as winner or loser forms of the protein. They report that, when human cells that express either FWE1 or FWE3 are cultured with cells that express either FWE2 or FWE4, cells that express FWE1 or FWE3 die and those that express FWE2 or FWE4 divide to compensate for the loss of the dying cells. Thus, in this system, cells that express FWE1 and FWE3 are loser cells and those that express FWE2 and FWE4 are winner cells. Loser cells undergo a type of cell death called apoptosis, and the initiation of cell death requires direct contact between winner and loser cells.<\/p>\n<p>The authors examined the expression of winner and loser versions of FWE in samples of human cancers. FWE<sup>Win<\/sup>\u00a0expression was higher in malignant tumours than in benign tumours. Madan and colleagues found that expression of FWE<sup>Lose<\/sup>\u00a0in normal cells adjacent to the tumour is higher than in normal cells farther away from it. Moreover, the level of FWE<sup>Lose<\/sup>\u00a0was higher in normal tissues adjacent to malignant tumours than in normal tissues that surrounded a benign tumour.<\/p>\n<p>When the authors transplanted human breast cancer cells that express FWE<sup>Win<\/sup>\u00a0into mice, the mouse cells adjacent to the transplanted tumour cells increased their expression of mouse FWE<sup>Lose<\/sup>\u00a0compared with the levels in animals that had not received a tumour transplant. All these results suggest that FWE<sup>Win<\/sup>\u00a0expression in tumour cells induces FWE<sup>Lose<\/sup>expression in neighbouring normal cells (Fig. 1). The mechanism responsible for such induction is unknown.<\/p>\n<p>&nbsp;<\/p>\n<figure class=\"figure\">\n<div class=\"embed intensity--high\">\n<div class=\"embed intensity--high\"><img decoding=\"async\" class=\"figure__image\" src=\"https:\/\/media.nature.com\/w800\/magazine-assets\/d41586-019-02161-y\/d41586-019-02161-y_16968940.png\" alt=\"\" data-src=\"\/\/media.nature.com\/w800\/magazine-assets\/d41586-019-02161-y\/d41586-019-02161-y_16968940.png\" \/><\/div>\n<\/div><figcaption>\n<p class=\"figure__caption sans-serif\"><span class=\"mr10\"><b>Figure 1 | Mammalian cell competition is driven by the expression of Flower protein.<\/b>\u00a0Different versions of a membrane protein called Flower (FWE) are made through a process called alternative splicing. These different versions are termed winner (FWE<sup>Win<\/sup>) or loser (FWE<sup>Lose<\/sup>), and they affect whether a cell survives or dies depending on which version of FWE is expressed by neighbouring cells. Madan\u00a0<i>et al<\/i>.<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-02161-y?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR3\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">3<\/a><\/sup>\u00a0studied human FWE in a type of cell called an epithelial cell, and investigated normal cells and cancer cells. Their results are consistent with the following model.\u00a0<b>a<\/b>, Tumour cells express FWE<sup>Win<\/sup>.\u00a0<b>b<\/b>, This leads, through an unknown mechanism, to the expression of FWE<sup>Lose<\/sup>\u00a0in neighbouring normal cells.\u00a0<b>c<\/b>, Competition between cells expressing FWE<sup>Win<\/sup>\u00a0or FWE<sup>Lose<\/sup>\u00a0results in the death of FWE<sup>Lose<\/sup>-expressing cells, and the FWE<sup>Win<\/sup>-expressing cells divide to fill the gap in the tissue that arises from this cell death.<\/span><\/p>\n<\/figcaption><\/figure>\n<p>The authors report that, when human breast cancer cells expressing FWE<sup>Win<\/sup>\u00a0were transplanted into the breast region of mice engineered to express human FWE<sup>Lose<\/sup>, the transplanted cells generated aggressive tumours. By contrast, less aggressive tumours were generated if FWE<sup>Lose<\/sup>-expressing human breast cancer cells were transplanted into mouse breast tissue that expressed human FWE<sup>Win<\/sup>. This indicates that it is the combination of high expression of FWE<sup>Win<\/sup>\u00a0in tumours and high expression of FWE<sup>Lose<\/sup>\u00a0in the tissue that surrounds them that aids cancer growth.<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>When the authors engineered human cancer cells to block expression of FWE and transplanted these cells into mouse legs, the cancer cells showed diminished growth and reduced capacity for migration (termed metastasis) to a secondary site compared with transplants of human cancer cells in which FWE expression was not blocked. When chemotherapy was also administered, growth of the engineered human cancer cells in the mouse legs was substantially inhibited.<\/p>\n<p>&nbsp;<\/p>\n<aside class=\"recommended pull pull--left sans-serif\" data-label=\"Related\"><a href=\"https:\/\/www.nature.com\/articles\/nature23534\" data-track=\"click\" data-track-label=\"recommended article\"><img decoding=\"async\" class=\"recommended__image\" src=\"https:\/\/media.nature.com\/w400\/magazine-assets\/d41586-019-02161-y\/d41586-019-02161-y_16971616.jpg\" \/><\/a><\/p>\n<p class=\"recommended__title serif\">Healthy skin rejects cancer<\/p>\n<\/aside>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>Madan and colleagues suggest that FWE should be investigated as a possible therapeutic target in human tumours and in the tissues that surround them. However, whether human FWE can be selectively targeted using antibodies or chemical compounds should be examined before a clinical approach can be considered.<\/p>\n<p>The authors have demonstrated convincingly that, in addition to its known role in\u00a0<i>D. melanogaster<\/i>, FWE also functions in cell competition in mammals. In both mammals and flies, the expression of FWE<sup>Lose<\/sup>\u00a0is induced in loser cells; cells expressing FWE<sup>Lose<\/sup>\u00a0die only if they encounter cells that express FWE<sup>Win<\/sup>; and it is the relative rather than the absolute levels of FWE<sup>Lose<\/sup>\u00a0and FWE<sup>Win<\/sup>\u00a0that trigger cell competition.<\/p>\n<p>Several issues remain to be addressed. For example, the regulatory proteins that act upstream or downstream of FWE have not been identified. What controls the alternative splicing that generates different forms of FWE is unknown, and understanding this process might reveal other therapeutic targets. Previous work<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-02161-y?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR4\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">4<\/a><\/sup>\u00a0suggests that membrane proteins of unknown identity can distinguish between winner and loser versions of FWE expressed on neighbouring cells. If such proteins exist, their identification will be necessary to understand how FWE-mediated cell competition functions.<\/p>\n<p>Another key question is whether cancer-promoting mutations trigger FWE-mediated cell competition in mammals, and, if so, which mutations are responsible. There are reports that abnormal expression of the tumour-promoting proteins Myc or Wnt is involved in FWE-related cell competition in\u00a0<i>D. melanogaster<\/i><sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-02161-y?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR4\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">4<\/a><\/sup><sup>\u2013<\/sup><sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-02161-y?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR6\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">6<\/a><\/sup>. Analyses of tumour cells from patients might shed light on whether this also occurs in humans.<\/p>\n<p>Madan and colleagues\u2019 work should motivate researchers to analyse human-tumour samples to determine the involvement of FWE in cell competition and cancer development. If antibodies could be developed to specifically recognize human FWE<sup>Lose<\/sup>\u00a0proteins, this would greatly aid such studies. However, generating such antibodies is not straightforward, and the authors discuss the technical hurdles that would need to be overcome.<\/p>\n<p>In\u00a0<i>D. melanogaster<\/i>, other proteins in addition to FWE can regulate cell competition<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-02161-y?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR7\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">7<\/a><\/sup><sup>,<\/sup><sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-02161-y?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR8\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">8<\/a><\/sup>, and further studies in human cancer cells will be needed to gain a more complete picture of mammalian cell competition. Such work might offer new perspectives for improving cancer treatments.<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<\/div>\n<div class=\"emphasis\">doi: 10.1038\/d41586-019-02161-y<\/div>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>(\uc6d0\ubb38: <a href=\"https:\/\/www.nature.com\/articles\/d41586-019-02161-y?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29\">\uc5ec\uae30<\/a>\ub97c \ud074\ub9ad\ud558\uc138\uc694~)<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>&nbsp; &nbsp; Cells compete for survival during development. It emerges that mammalian cells on a path to form a tumour express specific versions of the<a href=\"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=3933\" class=\"more-link\">(more&#8230;)<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2},"jetpack_post_was_ever_published":false},"categories":[33,29,30],"tags":[],"class_list":["post-3933","post","type-post","status-publish","format-standard","hentry","category-do-biology","category-lets-do-science","category-recent-science-news"],"aioseo_notices":[],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack-related-posts":[{"id":2523,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=2523","url_meta":{"origin":3933,"position":0},"title":"Cryptic DNA sequences may help cells survive starvation","author":"biochemistry","date":"January 18, 2019","format":false,"excerpt":"\u00a0 \u00a0 Stretches of non-coding DNA in genes called introns could have an important survival function. \u00a0 Non-coding 'intron' DNA can help yeast cells survive at times of stress.Credit: Michael Abbey\/Science Photo Library Patches of seemingly meaningless DNA dotted throughout the genome might actually have a function: helping cells to\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":4699,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=4699","url_meta":{"origin":3933,"position":1},"title":"Senescent cells feed on their neighbours","author":"biochemistry","date":"October 31, 2019","format":false,"excerpt":"\u00a0 Chemotherapy-treated cancer cells that enter a non-dividing state called senescence can nevertheless boost cancer growth. The finding that these cells eat neighbouring cells reveals a mechanism that enables senescent cells to persist. \u00a0 \u00a0 Multicellular life requires individual cells to cooperate in a way that benefits the organism. Cells\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":4084,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=4084","url_meta":{"origin":3933,"position":2},"title":"Scientists use gene-edited stem cells to treat HIV \u2014 with mixed success","author":"biochemistry","date":"September 17, 2019","format":false,"excerpt":"\u00a0 \u00a0 Modified cells survived 19 months after transplant into an HIV-positive man in China, but the dose was not enough to reduce his viral load. \u00a0 \u00a0 HIV destroys the body's defences by attacking immune cells.\u00a0Credit: Steve Gschmeissner\/Science Photo Library \u00a0 \u00a0 For the first time, researchers have used\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":3734,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=3734","url_meta":{"origin":3933,"position":3},"title":"Cell fate decisions during development","author":"biochemistry","date":"June 8, 2019","format":false,"excerpt":"\u00a0 \u00a0 The shape of our nose, the color of our skin, the movement of our gut, all depend on an extraordinary cell type called neural crest cells, which originate during embryogenesis. 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