[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-328996-105":59,"doc-detail-328996-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","unmasking-smlr1-the-hidden-player-in-colorectal-cancers-liver-metastasis","Unmasking SMLR1: The hidden player in colorectal cancer’s liver metastasis","","Unmasking SMLR1: The hidden player in colorectal cancer’s liver metastasis reviews how small leucine-rich protein 1 (SMLR1) contributes to colorectal cancer liver metastasis (CRLM). The work highlights SMLR1 upregulation in CRLM and its interaction with tumor-associated macrophages (TAMs) through MRC1 (CD206) and SIGLEC1 (CD169). By linking these molecular events to immune evasion, TAM polarization, and tumor progression in the liver microenvironment, the commentary frames SMLR1 as a potential therapeutic target while outlining key unresolved mechanisms and future validation directions.",{"@graph":69,"@context":122},[70,84,105],{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/unmasking-smlr1-the-hidden-player-in-colorectal-cancers-liver-metastasis/328996/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/unmasking-smlr1-the-hidden-player-in-colorectal-cancers-liver-metastasis/328996.png","ImageObject",300,407,{"name":92,"@type":93},"Riley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is SMLR1’s role in colorectal cancer liver metastasis (CRLM)?","Question",{"text":112,"@type":113},"SMLR1 is reported to be upregulated in CRLM and to support metastatic progression by engaging pathways that promote immune evasion.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does SMLR1 interact with tumor-associated macrophages?",{"text":117,"@type":113},"SMLR1 interacts with TAMs through MRC1 (CD206) and SIGLEC1 (CD169), driving TAM polarization toward an M2-like, pro-tumoral state.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is SMLR1 upregulation considered context-dependent?",{"text":121,"@type":113},"The text notes that SMLR1 upregulation was observed specifically in CRC liver metastases but not in CRC metastases at other sites such as the peritoneum.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},328996,1790482457,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":81,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":39},1374391975076,"https://ap-avatar.wpscdn.com/avatar/14000253ca4ec9f6853?x-image-process=image/resize,m_fixed,w_180,h_180&k=1783305029341752051","Author Manuscript Author Manuscript Author Manuscript Author Manuscript  \n\n| | HHS Public Access\u003Cbr>Author manuscript\u003Cbr>Cancer Heterog Plast. Author manuscript; available in PMC 2024 September 25. |\n| --- | --- |\n\nPublished in final edited form as:  \nCancer Heterog Plast. 2024 ; 1(1): . doi:10.47248/chp2401010002 .  \nUnmasking SMLR1: The hidden player in colorectal cancer’sliver metastasis  \nXiaozhuo Liu  \nDepartment of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA  \nExploring cancer cell adaptability and the complexity of the tumor microenvironment (TME) is both fascinating and crucial in cancer research. During metastasis, cancer cells must undergo significant changes to adapt and survive in new environment. For colorectal cancer, the liver is a primary site of metastasis. Understanding why certain cancers preferentially spread to specific organs, such as the liver, can provide insights into tumor biology and inform new therapeutic strategies.  \nIn this inaugural issue of Cancer Heterogeneity and Plasticity, Wong and colleagues present novel roles of small leucine-rich protein 1 (SMLR1) in colorectal cancer liver metastasis (CRLM). By demonstrating that SMLR1 is upregulated in CRLM and interacts with tumor-associated macrophages (TAMs) via MRC1 (CD206) and SIGLEC1 (CD169), this research unveils a novel mechanism of immune evasion and tumor progression. Notably, SMLR1 upregulation was observed specifically in the CRC liver metastases but not in CRC metastases in other tissues such as the peritoneum (see Figure 1), suggesting a contextdependent interaction between cancer cells and the liver microenvironment that facilitates metastasis.  \nThis study aligns well with the mission of Cancer Heterogeneity and Plasticity by exploring the dynamic realm of cancer cell heterogeneity and the complexity and cellular cross-talks in the TME. The elucidation of SMLR1’s role in immune evasion and metastasis contributes valuable insights into cancer cell plasticity and reprogramming. The focus on specific molecular interactions in the liver microenvironment exemplifies the type of research that can drive forward our understanding of cancer adaptability.  \nWhile the study provides significant insights, there are areas that require further exploration. The mechanisms underlying SMLR1 upregulation in CRLM remain unclear and warrant  \nThis is an Open Access article distributed under the Creative Commons License Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is correctly credited.  \n[Xiaozhuo.Liu@Roswellpark.org](Xiaozhuo.Liu@Roswellpark.org) .  \nEthics Statement Not applicable.  \nConsent for Publication Not applicable.  \nCompeting Interests  \nThe author has declared that no competing interests exist.  \nAuthor Manuscript Author Manuscript Author Manuscript Author Manuscript  \nLiu Page 2  \nadditional investigation. Moreover, the therapeutic potential of targeting SMLR1 should be explored in vivo to assess efficacy and safety. It would also be interesting to investigate whether lung metastasis exhibits a similar pattern of SMLR1 upregulation and interaction with the microenvironment as seen in liver metastasis or ifit resembles peritoneum metastasis. Future studies could broaden the scope of clinical relevance by examining SMLR1 upregulation in other metastatic sites and cancer types.  \nAcknowledgments  \nI thank the Editor-in-Chief, Professor Dean Tang, for the invitation and opportunity to contribute to the inaugural issue of Cancer Heterogeneity and Plasticity. Special thanks also to the editorial office, particularly Ms. Evelyn Liang, for her assistance throughout the editorial process. Finally, I acknowledge BioRender, which was used to generate the graphical representation of my Commentary.  \nAvailability of Data and Material  \nNot applicable.  \nReferences  \n1. Wong CW, Wang L, ","cbCaio0exeRV0oW0","https://ap.wps.com/l/cbCaio0exeRV0oW0","pdf",350876,"English","# Introduction\n# SMLR1 roles in CRLM and immune evasion\n# Research implications and future directions","[{\"question\":\"What is SMLR1’s role in colorectal cancer liver metastasis (CRLM)?\",\"answer\":\"SMLR1 is reported to be upregulated in CRLM and to support metastatic progression by engaging pathways that promote immune evasion.\"},{\"question\":\"How does SMLR1 interact with tumor-associated macrophages?\",\"answer\":\"SMLR1 interacts with TAMs through MRC1 (CD206) and SIGLEC1 (CD169), driving TAM polarization toward an M2-like, pro-tumoral state.\"},{\"question\":\"Why is SMLR1 upregulation considered context-dependent?\",\"answer\":\"The text notes that SMLR1 upregulation was observed specifically in CRC liver metastases but not in CRC metastases at other sites such as the peritoneum.\"}]","Unmasking SMLR1: The hidden player in colorectal cancer’s liver metastasis | PDF",1789982005]