{"id":14277,"date":"2015-01-25T15:55:27","date_gmt":"2015-01-25T21:55:27","guid":{"rendered":"http:\/\/www.salud.carlosslim.org\/english2\/?p=14277"},"modified":"2015-01-27T13:09:28","modified_gmt":"2015-01-27T19:09:28","slug":"enzymes-believed-promoting-cancer-actually-suppress-tumors","status":"publish","type":"post","link":"http:\/\/www.salud.carlosslim.org\/english2\/enzymes-believed-promoting-cancer-actually-suppress-tumors\/","title":{"rendered":"Enzymes Believed Promoting Cancer Actually Suppress Tumors"},"content":{"rendered":"

\"20A team of scientists at the School of Medicine of the University of California – San Diego (UCSD), just overthrown a decades-old dogma when finding that enzymes which were long categorized as promoters of cancer are actually tumor suppressors<\/strong>. According with the researchers, current clinical efforts to develop inhibitor-based drugs should instead focus on restoring the enzymes\u2019 activities.<\/p>\n

Protein Kinase C (PKC) is a group of enzymes that act as catalysts for a host of cellular function<\/strong>s, among which are cancer-relevant activities<\/strong>, such as cell survival, proliferation, apoptosis, and migration. The discovery that they are receptors for tumor-producing phorbol esters, plant-derived compounds that bind to and activate PKC, created a dogma that activation of PKCs by phorbol esters promoted carcinogen-induced tumorigenesis.<\/p>\n

\u201cFor three decades, researchers have sought to find new cancer therapies based on the idea that inhibiting or blocking PKC signals would hinder or halt tumor development,\u201d said Alexandra Newton, PhD, professor of pharmacology and the study\u2019s principal investigator,<\/em> \u201cbut PKCs have remained an elusive chemotherapeutic target.\u201d The reason, suggest Newton and colleagues, is that contrary to conventional wisdom, PKCs do not promote cancer progression; rather, they act to suppress tumor growth.<\/p>\n

Using live cell imaging, first author Corina Antal, a graduate student in the Biomedical Sciences program at UC San Diego, characterized 8 percent of the more than 550 PKC mutations identified in human cancers. This led to the unexpected discovery that the majority of mutations actually reduced or abolished PKC activity<\/strong>, and none were activating. The mutations impeded signal binding, prevented correct structuring of the enzyme, or impaired catalytic activity.<\/p>\n

When the scientists corrected a loss-of-function PKC mutation in the genome of a colon cancer cell line, tumor growth in a mouse model was reduced, demonstrating that normal PKC activity inhibits cancer. One possible explanation, said the researchers, is that PKC typically represses signaling from certain oncogenes \u2013 genes that can cause normal cells to become cancerous. When PKC is lost, oncogenic signaling increases, fueling tumor growth.<\/p>\n

\u201cInhibiting PKC has so far proved not only an unsuccessful strategy in a number of cancer clinical trials, but its addition to chemotherapy has resulted in decreased response rates in patients,\u201d<\/em> said Newton. \u201cGiven our results, this isn\u2019t surprising. Our findings suggest therapeutic strategies need to go the other way and target ways to restore PKC activity, not inhibit it. This is contrary to the current dogma.\u201d<\/em><\/p>\n

How could this misconception of PKC promoting tumors have arisen?<\/p>\n

Acording with Corina Antal, long-term activation of PKCs by phorbol esters results in their degradation. In models of tumor promotion, a sub-threshold dose of a carcinogen is painted on mouse skin, followed by repeated applications of phorbol esters. \u201cThis repeated application of phorbol esters will lead to the loss of PKC. Thus, their tumor-promoting function may arise because a brake to oncogenic signaling has been removed.\u201d<\/em><\/p>\n

The findings are published in the January 29 issue of Cell<\/em>.<\/p>\n

Source:<\/strong> UC San Diego News Center<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

A team of scientists at the School of Medicine of the University of California – San Diego (UCSD), just overthrown a decades-old dogma when finding that enzymes which were long categorized as promoters of cancer are actually tumor suppressors. According with the researchers, current clinical efforts to develop inhibitor-based drugs should instead focus on restoring …<\/p>\n","protected":false},"author":1,"featured_media":9841,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"ngg_post_thumbnail":0,"footnotes":""},"categories":[3],"tags":[12],"class_list":["post-14277","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-actualidad-en-la-salud","tag-genomica","cat-3-id","has_thumb"],"_links":{"self":[{"href":"http:\/\/www.salud.carlosslim.org\/english2\/wp-json\/wp\/v2\/posts\/14277","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/www.salud.carlosslim.org\/english2\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/www.salud.carlosslim.org\/english2\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/www.salud.carlosslim.org\/english2\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/www.salud.carlosslim.org\/english2\/wp-json\/wp\/v2\/comments?post=14277"}],"version-history":[{"count":2,"href":"http:\/\/www.salud.carlosslim.org\/english2\/wp-json\/wp\/v2\/posts\/14277\/revisions"}],"predecessor-version":[{"id":14303,"href":"http:\/\/www.salud.carlosslim.org\/english2\/wp-json\/wp\/v2\/posts\/14277\/revisions\/14303"}],"wp:featuredmedia":[{"embeddable":true,"href":"http:\/\/www.salud.carlosslim.org\/english2\/wp-json\/wp\/v2\/media\/9841"}],"wp:attachment":[{"href":"http:\/\/www.salud.carlosslim.org\/english2\/wp-json\/wp\/v2\/media?parent=14277"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/www.salud.carlosslim.org\/english2\/wp-json\/wp\/v2\/categories?post=14277"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/www.salud.carlosslim.org\/english2\/wp-json\/wp\/v2\/tags?post=14277"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}