{"id":8085,"date":"2020-12-01T10:11:21","date_gmt":"2020-12-01T10:11:21","guid":{"rendered":"https:\/\/www.innovationnewsnetwork.com\/?p=8085"},"modified":"2020-12-01T10:11:43","modified_gmt":"2020-12-01T10:11:43","slug":"understanding-the-aggressive-spread-of-prostate-cancer-cells","status":"publish","type":"post","link":"https:\/\/www.innovationnewsnetwork.com\/understanding-the-aggressive-spread-of-prostate-cancer-cells\/8085\/","title":{"rendered":"Understanding the aggressive spread of prostate cancer cells"},"content":{"rendered":"<h2>A five-year study into the mechanisms by which cancer cells become mobile and start spreading has implications for the way in which aggressive prostate cancer is treated in the future.<\/h2>\n<p>Previous studies into the aggressive spread of cancers, including prostate cancer, have shown an overproduction of TGF-\u03b2, which regulates how cells grow and specialise in many cancer forms. High levels of TGF-\u03b2 are strongly linked with poor prognosis and low survival rates because the growth factor stimulates cancer cells to spread in the human body, causing <a href=\"https:\/\/www.innovationnewsnetwork.com\/prostate-cancer-secondary-tumours\/6766\/\">life-threatening secondary tumours<\/a>. TGF-\u03b2 regulates the expression of the protein Smad7, an active component in the TGF-\u03b2 signalling chain; and in healthy cells, Smad7 can prevent continued TGF-\u03b2 signalling via negative feedback.<\/p>\n<p>The team behind the study, led by Professor Mar\u00e9ne Landstr\u00f6m at the Department of Medical Biosciences at Ume\u00e5 University, includes former postdoc students Noopur Thakur and Anahita Hamidi; PhD and postdoc student, Jie Song; Susumu Itoh, a Professor at the Laboratory of Biochemistry, Showa Pharmaceutical University, Japan; Anders Bergh, a Professor at the Department of Medical Biosciences at Ume\u00e5 University, and Professor Carl-Henrik Heldin from Uppsala University, Sweden. Professor Landstr\u00f6m explains how the research conducted by her team has revealed that, in cancer cells, Smad7 can reinforce the development of tumours by regulating the gene expression of HDAC6 and c-Jun. The findings of the study could be used to develop more precise treatment strategies for aggressive prostate cancer in the future.<\/p>\n<h3>What were the drivers for the study and what questions did you hope to answer?<\/h3>\n<p>The study originated with the hypothesis that Smad7 could take an active part in gene transcription in response to the TGF-\u03b2 stimulation of prostate cancer cells, as we had previously made the unexpected original finding that Smad7 could shuttle between the nucleus and cytoplasm. When the Smad7 gene was found, Smad7 was classified as an inhibitory Smad; this meant that it could inhibit TGF-\u03b2 signalling.<\/p>\n<p>We set out to explore if Smad7 could have additional unknown roles to affect gene regulation and to find out the potential role of Smad7 in the nucleus; looking at whether Smad7 could have a positive role to play in TGF-\u03b2 induced gene regulation.<\/p>\n<h3>Why are high levels of TGF-\u03b2 strongly linked with poor prognosis and low survival rates in certain forms of cancer?<\/h3>\n<p>High levels of TGF-\u03b2 have been shown to correlate with poor prognosis for patients affected by many different kinds of cancer. TGF-\u03b2 transforms normal epithelial cells to become mesenchymal, migratory, and invasive. TGF-\u03b2 also promotes changes in the tumour stroma so that cancer-associated fibroblasts are attracted to become a part of the tumour stroma. Tumour cells produce TGF-\u03b2 in an autocrine manner. TGF-\u03b2 is also produced by stromal cells. High levels of TGF-\u03b2 affect the immune response so that immune cells cannot recognise and destroy the tumour cells.<\/p>\n<h3>What is Smad7 and how does it reinforce the development of tumours?<\/h3>\n<p>Smad7 is an adaptor protein which can bind to the TGF-\u03b2 Type I receptor activin like kinase 5 (ALK5) to prevent further TGF-\u03b2 signalling; it can also promote the activation of the TGF-\u03b2- TAK1 \u2013p38MAPK\/JNK-pathway to promote migratory responses, apoptosis, and the dedifferentiation of cells. We show in our paper (<a href=\"https:\/\/www.cell.com\/iscience\/pdf\/S2589-0042(20)30662-3.pdf\" target=\"_blank\" rel=\"noopener noreferrer\">Thakur <em>et al<\/em>., 2020<\/a>) that in the nucleus, Smad7 can act as a transcriptional regulator of c-Jun and HDAC6 to promote migratory and invasive responses of prostate cancer cells. How this occurs is not yet fully understood, but I believe that it is through its activation of c-Jun and HDAC6.<\/p>\n<h3>What were the main findings\/outcomes of the study and how did it show an entirely new function of Smad7?<\/h3>\n<p>The key finding of the study was that we could identify two consensus binding sites in DNA for Smad7 for the regulation of c-Jun and HDAC6. Moreover, we could also identify a specific amino acid in the N-terminal part of Smad7 that was necessary for binding to DNA (K102). The fact that we can identify on the amino-acid level that Smad7 can act as a transcription factor is novel knowledge.<\/p>\n<h3>Did you face any challenges and, if so, how were these overcome?<\/h3>\n<p>We initially sent our paper to an established journal and while we had received very positive comments from our reviewers the journal didn\u2019t accept the paper. It took us some time to get our novel findings accepted for publication in iScience and we expect it to attract a significant level of interest as it reveals a previously unknown function for Smad7.<\/p>\n<h3>What implications will the findings of the study have for the treatment of aggressive prostate cancer in the future, and how will this study inform future studies?<\/h3>\n<p>We hope that it will add novel knowledge that can lead to better and more precise treatment strategies for patients with prostate cancer in the future and I expect that our study will open a new field of research within the field of TGF-\u03b2 and tumour biology.<\/p>\n<p>Clinical trials are currently taking place in the UK with the goal of finding specific HDAC6 inhibitors in patients with solid tumours in order to develop future treatments using HDAC6 inhibitors to be deployed alongside <a href=\"https:\/\/www.innovationnewsnetwork.com\/prostate-cancer-diagnosis-treatment-and-research\/6093\/\">existing treatment protocols<\/a> for patients with hard-to-treat forms of the disease, but we do not yet know the outcome of these trials.<\/p>\n<p><strong>Professor Mar\u00e9ne Landstr\u00f6m<\/strong><br \/>\n<strong>Senior Consultant and (Attending) Physician<\/strong><br \/>\n<strong>Department of Medical Biosciences<\/strong><br \/>\n<strong>Ume\u00e5 University<\/strong><br \/>\n<strong>+46 90 785 24 58<\/strong><br \/>\n<strong><a href=\"mailto:marene.landstrom@umu.se\">marene.landstrom@umu.se<\/a><\/strong><br \/>\n<strong>Tweet <a href=\"https:\/\/twitter.com\/umeauniversity\" target=\"_blank\" rel=\"noopener noreferrer\">@umeauniversity<\/a><\/strong><br \/>\n<strong><a href=\"http:\/\/www.umu.se\/en\/department-of-medical-biosciences\" target=\"_blank\" rel=\"noopener noreferrer\">www.umu.se\/en\/department-of-medical-biosciences<\/a><\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"<p>A five-year study into the mechanisms by which cancer cells become mobile and start spreading has implications for the way in which aggressive prostate cancer is treated in the future. Previous studies into the aggressive spread of cancers, including prostate cancer, have shown an overproduction of TGF-\u03b2, which regulates how cells grow and specialise in [&hellip;]<\/p>\n","protected":false},"author":3,"featured_media":8087,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[10551],"tags":[768,529,580,22750],"acf":[],"yoast_head":"\n<title>Understanding the aggressive spread of prostate cancer cells<\/title>\n<meta name=\"description\" content=\"A five-year study into the mechanisms by which cancer cells start spreading has implications for the treatment of aggressive prostate cancer.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.innovationnewsnetwork.com\/understanding-the-aggressive-spread-of-prostate-cancer-cells\/8085\/\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Understanding the aggressive spread of prostate cancer cells\" \/>\n<meta property=\"og:description\" content=\"A five-year study into the mechanisms by which cancer cells start spreading has implications for the treatment of aggressive prostate cancer.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.innovationnewsnetwork.com\/understanding-the-aggressive-spread-of-prostate-cancer-cells\/8085\/\" \/>\n<meta property=\"og:site_name\" content=\"Innovation News Network\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/InnoNewsNetwork\" \/>\n<meta property=\"article:published_time\" content=\"2020-12-01T10:11:21+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2020-12-01T10:11:43+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.innovationnewsnetwork.com\/wp-content\/uploads\/2020\/12\/UMEAUNI3-26770-image-2.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1920\" \/>\n\t<meta property=\"og:image:height\" content=\"1080\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Rosemary Lobley\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@InnoNewsNetwork\" \/>\n<meta name=\"twitter:site\" content=\"@InnoNewsNetwork\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Rosemary Lobley\" \/>\n\t<meta name=\"twitter:label2\" content=\"Estimated reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"5 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\/\/www.innovationnewsnetwork.com\/understanding-the-aggressive-spread-of-prostate-cancer-cells\/8085\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.innovationnewsnetwork.com\/understanding-the-aggressive-spread-of-prostate-cancer-cells\/8085\/\"},\"author\":{\"name\":\"Rosemary Lobley\",\"@id\":\"https:\/\/www.innovationnewsnetwork.com\/#\/schema\/person\/82292d2d812b0dca1b998dc4dbd79fb9\"},\"headline\":\"Understanding the aggressive spread of prostate cancer cells\",\"datePublished\":\"2020-12-01T10:11:21+00:00\",\"dateModified\":\"2020-12-01T10:11:43+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.innovationnewsnetwork.com\/understanding-the-aggressive-spread-of-prostate-cancer-cells\/8085\/\"},\"wordCount\":917,\"commentCount\":0,\"publisher\":{\"@id\":\"https:\/\/www.innovationnewsnetwork.com\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.innovationnewsnetwork.com\/understanding-the-aggressive-spread-of-prostate-cancer-cells\/8085\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.innovationnewsnetwork.com\/wp-content\/uploads\/2020\/12\/UMEAUNI3-26770-image-2.jpg\",\"keywords\":[\"Cancer\",\"Contributor Profile\",\"Diseases &amp; 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