{"id":16695,"date":"2019-08-08T09:34:55","date_gmt":"2019-08-08T09:34:55","guid":{"rendered":"https:\/\/www.revoscience.com\/en\/?p=16695"},"modified":"2020-06-09T12:42:28","modified_gmt":"2020-06-09T12:42:28","slug":"deciphering-pancreatic-cancers-invade-and-evade-tactics","status":"publish","type":"post","link":"https:\/\/www.revoscience.com\/en\/deciphering-pancreatic-cancers-invade-and-evade-tactics\/","title":{"rendered":"Deciphering pancreatic cancer\u2019s invade and evade tactics"},"content":{"rendered":"\n
\"\"<\/figure>\n\n\n\n

Two known gene mutations induce pathways that enhance pancreatic cancer\u2019s ability to invade tissues and evade the immune system. <\/p>\n\n\n\n

Two known gene mutations induce pathways that enhance pancreatic cancer\u2019s ability to invade tissues and evade the immune system. <\/p>\n\n\n\n

Researchers report the molecular details of this process providing insights into druggable targets for immunotherapies.<\/p>\n\n\n\n

Mutations in the genes\u00a0KRAS<\/em>\u00a0and\u00a0TP53<\/em>\u00a0are closely linked to pancreatic ductal adenocarcinoma, by far the most common type of pancreatic cancer. <\/p>\n\n\n\n

Pancreatic cancers are often already malignant when diagnosed, making its five-year survival rate extremely low \u2014 less than ten percent. So, understanding how it evolves at the molecular level could help anti-cancer drug development.<\/p>\n\n\n\n

Hisataka Sabe of Hokkaido University and colleagues in Japan conducted tests in human cancer cells and in mouse models of the disease to investigate the roles of\u00a0KRAS<\/em>\u00a0and\u00a0TP53<\/em>\u00a0gene mutations in pancreatic ductal adenocarcinoma. The study was published in the journal\u00a0Proceedings of the National Academy of Sciences (PNAS)<\/em>.<\/p>\n\n\n\n

They found that mutations in\u00a0KRAS<\/em>\u00a0increased the production of two proteins, called ARF6 and AMAP1, which they previously discovered constitute a signalling pathway involved in cancer cell invasion and malignancy.<\/p>\n\n\n\n

Mutations in the gene\u00a0TP53<\/em>\u00a0were also found to facilitate ARF6 activation, in addition to causing a metabolic pathway, called the mevalonate pathway, to go into overdrive. This pathway is known for its role in enhancing the invasiveness of some cancers.<\/p>\n\n\n\n

Further investigations of the ARF6-AMAP1 pathway found it was involved in promoting cell-surface expression of an immune checkpoint protein, called PD-L1, on cancer cells, in addition to enhancing its recycling within the cell. PD-L1 expression on cancer cells helps them hide from the immune system, avoiding attack. Mutated\u00a0KRAS<\/em>\u00a0and\u00a0TP53<\/em>\u00a0genes, and over-activation of the mevalonate pathway, both played crucial roles in the eventual cell-surface expression and recycling of PD-L1.<\/p>\n\n\n\n

\u201cWe found that two well-known driver mutations of pancreatic cancer can promote both invasion to other tissues and evasion of the immune system through promoting the ARF6 pathway. <\/p>\n\n\n\n

This means that malignancies can develop in parallel with oncogenesis, making it difficult to detect cancer cells in its early stage,\u201d says Hisataka Sabe. <\/p>\n\n\n\n

\u201cFurther studies are still needed to determine the extent of PD-L1 involvement in immune evasion. Studies are also needed to consider if PD-L1- and ARF6-targeting drugs can make pancreatic cancer cells more susceptible to attack by the immune system,\u201d he continued.<\/p>\n

TAGS: <\/strong>Research<\/a> <\/div>","protected":false},"excerpt":{"rendered":"

Researchers report the molecular details of this process providing insights into druggable targets for immunotherapies.<\/p>\n","protected":false},"author":2,"featured_media":16696,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[26,17],"tags":[112],"class_list":["post-16695","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicine","category-research","tag-research"],"featured_image_urls":{"full":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1.jpg",800,480,false],"thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1-200x200.jpg",200,200,true],"medium":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1-300x180.jpg",300,180,true],"medium_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1-768x461.jpg",750,450,true],"large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1.jpg",750,450,false],"1536x1536":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1.jpg",800,480,false],"2048x2048":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1.jpg",800,480,false],"ultp_layout_landscape_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1.jpg",800,480,false],"ultp_layout_landscape":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1.jpg",800,480,false],"ultp_layout_portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1.jpg",600,360,false],"ultp_layout_square":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1.jpg",600,360,false],"newspaper-x-single-post":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1-760x480.jpg",760,480,true],"newspaper-x-recent-post-big":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1-550x360.jpg",550,360,true],"newspaper-x-recent-post-list-image":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1-95x65.jpg",95,65,true],"web-stories-poster-portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1.jpg",640,384,false],"web-stories-publisher-logo":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1.jpg",96,58,false],"web-stories-thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2019\/08\/pancreaticis1.jpg",150,90,false]},"author_info":{"info":["RevoScience"]},"category_info":"Medicine<\/a> Research<\/a>","tag_info":"Research","comment_count":"0","_links":{"self":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/16695","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/comments?post=16695"}],"version-history":[{"count":0,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/16695\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media\/16696"}],"wp:attachment":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media?parent=16695"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/categories?post=16695"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/tags?post=16695"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}