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LY-290181 was evaluated in breast cancer cell lines and shown to dose-dependently suppress migration, invasion, and multicellular tumor spheroid invasion. These anti-cancer effects were mediated by down-regulating Twist1 protein levels and inhibiting ERK and JNK signaling pathways. Results support LY-290181 as a foundation for further research and development of metastatic cancer therapeutics targeting Twist1.",{"@graph":69,"@context":121},[70,84,104],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/anti-migration-and-anti-invasion-effects-of-ly-290181-on-breast-cancer-cell-lines-through-the-inhibition-of-twist1/377060/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/anti-migration-and-anti-invasion-effects-of-ly-290181-on-breast-cancer-cell-lines-through-the-inhibition-of-twist1/377060.png","ImageObject",300,407,{"name":92,"@type":93},"Quinn Holloway","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24",true,{"@type":101,"interactionType":102,"userInteractionCount":14},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"What is the main goal of the study described in the text?","Question",{"text":111,"@type":112},"To investigate how LY-290181 affects anti-metastatic behaviors in breast cancer cell lines and to identify mechanisms involving Twist1 inhibition.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"How does LY-290181 impact migration and invasion in breast cancer cells?",{"text":116,"@type":112},"LY-290181 dose-dependently inhibits migration and invasion, including invasion of multicellular tumor spheroids.",{"name":118,"@type":109,"acceptedAnswer":119},"Which molecular pathway and regulator mediate LY-290181’s anti-cancer effects?",{"text":120,"@type":112},"The effects are mediated through down-regulation of Twist1 protein levels and inhibition of ERK and JNK signaling pathways, suppressing EMT marker regulation.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},377060,1790247211,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":29,"language":138,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":139,"faqs":140,"seo_title":141,"seo_description":67,"update_tm":142,"read_time":143},2336474466712,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","BMB Reports  \nBMB Rep. 2023; 56(7): 410-415  \n[www.bmbreports.org](www.bmbreports.org)  \nAnti-migration and anti-invasion effects ofLY-290181 on breast cancer cell lines through the inhibition of Twist1  \nJiyoung Park, Sewoong Lee, Haelim Yoon, Eunjeong Kang & Sayeon Cho * College of Pharmacy, Chung-Ang University, Seoul 06974, Korea  \nBreast cancer has become the most common cancer among women worldwide. Among breast cancers, metastatic breast cancer is associated with the highest mortality rate. Twist1, one of the epithelial-mesenchymal transition-regulating transcription factors, is known to promote the intravasation of breast cancer cells into metastatic sites. Therefore, targeting Twist1 to develop anti-cancer drugs might be a valuable strategy. In this study, LY-290181 dose-dependently inhibited migration, invasion, and multicellular tumor spheroid invasion in breast cancer cell lines. These anti-cancer effects of LY-290181 were mediated through the down-regulation of Twist1 protein levels. LY-290181 inhibited extracellular signal-regulated kinaseand c-Jun N-terminal kinase signaling pathways. Therefore, our findings suggest that LY-290181 may serve as a basis for future research and development of an anti-cancer agent targeting metastatic cancers. [BMB Reports 2023; 56(7): 410-415]  \nINTRODUCTION  \nBreast cancer has become the leading cause of death from cancer in women, overtaking lung cancer, which was the most diagnosed cancer in the past two decades (1) . Breast cancer usually metastasizes to the lungs, bones, liver, and brain (2) . Systemic therapy is the main treatment option for metastatic breast cancer and is associated with significant improvements in survival rate (3) . Chemotherapy shrinks cancerous tumorsand prolongs the lifespan of patients but has several side effects, such as premature menopause and hair thinning (2) . Therefore, it is necessary to develop novel drugs to achieve effective inhibition of breast cancer metastasis.  \nMetastasis is promoted by epithelial-mesenchymal transition (EMT), a process through which epithelial cells transform into mesenchymal cells with metastatic and invasive abilities (4) .  \n*Corresponding author. Tel: +82-2-820-5595; Fax: +82-2-816-7338; E-mail: [sycho@cau.ac.kr](sycho@cau.ac.kr)  \n[https://doi.org/10.5483/BMBRep.2023-0011](https://doi.org/10.5483/BMBRep.2023-0011)  \nReceived 30 January 2023, Revised 4 April 2023,  \nAccepted 20 June 2023, Published online 28 June 2023  \nKeywords: Breast cancer, EMT, LY-290181, TNBC, Twist1  \nEMT has been extensively studied in relation to angiogenesis, organogenesis, and metastasis (5) . EMT-regulating transcription factors (EMT-TFs), the regulators of the EMT process, include Snail1, ZEB1, and Twist1 (6) . These EMT-TFs down-regulate the expression of epithelial markers such as E-cadherin and occludin while up-regulating the expression of mesenchymal markers such as N-cadherin and vimentin (7) . High expression levels of EMT-TFs have been reported to be associated with multiple types of aggressive cancer such as breast, liver, gastric, and pancreatic cancers (5) . EMT-TFs are regulated by a variety of intracellular signaling pathways, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 (8) . These signaling pathways play a role in the onset, progression, and poor prognosis of breast cancer and are therefore considered important targets for cancer therapy (9, 10) .  \nTwist1, a basic helix-loop-helix domain-containing transcription factor, is a key regulator of the mesenchymal phenotype (11) . The most important role of Twist1 is to promote EMT to induce distant metastasis of cancer cells endowed with highly invasive and aggressive properties (12) . Twist1, which is activated in several aggressive carcinomas, exhibits an inverse correlation with E-cadherin expression to promote tumor metastasis (11) . Several studies on the correlation between Twist1 and breast cancer metastasis have been re","cbCaijFa3UxNfgwn","https://ap.wps.com/l/cbCaijFa3UxNfgwn","pdf",10553814,"English","# Introduction\n## EMT and Twist1 in breast cancer metastasis\n## Rationale for targeting Twist1\n## Background on LY-290181","[{\"question\":\"What is the main goal of the study described in the text?\",\"answer\":\"To investigate how LY-290181 affects anti-metastatic behaviors in breast cancer cell lines and to identify mechanisms involving Twist1 inhibition.\"},{\"question\":\"How does LY-290181 impact migration and invasion in breast cancer cells?\",\"answer\":\"LY-290181 dose-dependently inhibits migration and invasion, including invasion of multicellular tumor spheroids.\"},{\"question\":\"Which molecular pathway and regulator mediate LY-290181’s anti-cancer effects?\",\"answer\":\"The effects are mediated through down-regulation of Twist1 protein levels and inhibition of ERK and JNK signaling pathways, suppressing EMT marker regulation.\"}]","Anti-migration and anti-invasion effects of LY-290181 on breast cancer cell lines through the inhibition of Twist1 | PDF",1790222914,15]