LGR5: An emerging therapeutic target for cancer metastasis and chemotherapy resistance.

IF 7.7 2区医学 Q1 ONCOLOGY

Cancer and Metastasis Reviews Pub Date : 2025-01-17 DOI:10.1007/s10555-024-10239-x

Wanqi Wang, Noor A Lokman, Simon C Barry, Martin K Oehler, Carmela Ricciardelli

{"title":"LGR5: An emerging therapeutic target for cancer metastasis and chemotherapy resistance.","authors":"Wanqi Wang, Noor A Lokman, Simon C Barry, Martin K Oehler, Carmela Ricciardelli","doi":"10.1007/s10555-024-10239-x","DOIUrl":null,"url":null,"abstract":"<p><p>Cancer stem cells play an important role in tumor progression and chemotherapy resistance. Leucine-rich G repeat-containing protein-coupled receptor 5 (LGR5) has been identified as a cancer stem cell marker in several cancer types. LGR5 is involved in cancer development and progression via several pathways including WNT/β-catenin signaling pathway. LGR5 plays a role in tumor progression by promoting cancer cell migration, invasion, metastasis, and angiogenesis in many cancers including colorectal, brain, gastric, and ovarian cancer. This review summarises the current knowledge on the expression and functional role of LGR5 in cancers, the molecular mechanisms regulated by LGR5, and the relationship between LGR5 and chemotherapy resistance. The review also includes highlights potential strategies to inhibit LGR5 expression and function. The majority of functional studies have shown that LGR5 plays an important role in promoting cancer progression, metastasis and chemotherapy resistance however, in some contexts LGR5 can also activate tumor-suppressive pathways and LGR5 negative cells can also promote cancer progression. The review highlights that targeting LGR5 is a promising anti-cancer treatment but the functional effect of LGR5 on tumor cells is complex may be dependent on cancer type, tumor microenvironment and cross-talk with other molecules in the LGR5 signaling pathway.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 1","pages":"23"},"PeriodicalIF":7.7000,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742290/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer and Metastasis Reviews","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10555-024-10239-x","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Cancer stem cells play an important role in tumor progression and chemotherapy resistance. Leucine-rich G repeat-containing protein-coupled receptor 5 (LGR5) has been identified as a cancer stem cell marker in several cancer types. LGR5 is involved in cancer development and progression via several pathways including WNT/β-catenin signaling pathway. LGR5 plays a role in tumor progression by promoting cancer cell migration, invasion, metastasis, and angiogenesis in many cancers including colorectal, brain, gastric, and ovarian cancer. This review summarises the current knowledge on the expression and functional role of LGR5 in cancers, the molecular mechanisms regulated by LGR5, and the relationship between LGR5 and chemotherapy resistance. The review also includes highlights potential strategies to inhibit LGR5 expression and function. The majority of functional studies have shown that LGR5 plays an important role in promoting cancer progression, metastasis and chemotherapy resistance however, in some contexts LGR5 can also activate tumor-suppressive pathways and LGR5 negative cells can also promote cancer progression. The review highlights that targeting LGR5 is a promising anti-cancer treatment but the functional effect of LGR5 on tumor cells is complex may be dependent on cancer type, tumor microenvironment and cross-talk with other molecules in the LGR5 signaling pathway.

查看原文本刊更多论文

LGR5：肿瘤转移和化疗耐药的新靶点

肿瘤干细胞在肿瘤进展和化疗耐药中起着重要作用。富含亮氨酸的G重复序列蛋白偶联受体5 （LGR5）已被确定为几种癌症类型的癌症干细胞标志物。LGR5通过多种途径参与癌症的发生和进展，包括WNT/β-catenin信号通路。LGR5在包括结直肠癌、脑癌、胃癌和卵巢癌在内的许多癌症中，通过促进癌细胞迁移、侵袭、转移和血管生成，在肿瘤进展中发挥作用。本文就LGR5在肿瘤中的表达和功能作用、LGR5调控的分子机制以及LGR5与化疗耐药的关系等方面的研究进展进行综述。该综述还重点介绍了抑制LGR5表达和功能的潜在策略。大多数功能研究表明，LGR5在促进肿瘤进展、转移和化疗耐药中发挥重要作用，但在某些情况下，LGR5也可以激活肿瘤抑制通路，LGR5阴性细胞也可以促进癌症进展。综述强调，靶向LGR5是一种很有前景的抗癌治疗方法，但LGR5对肿瘤细胞的功能作用是复杂的，可能取决于肿瘤类型、肿瘤微环境以及LGR5信号通路中其他分子的串扰。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cancer and Metastasis Reviews 医学-肿瘤学

CiteScore

17.00

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Contemporary biomedical research is on the threshold of an era in which physiological and pathological processes can be analyzed in increasingly precise and mechanistic terms.The transformation of biology from a largely descriptive, phenomenological discipline to one in which the regulatory principles can be understood and manipulated with predictability brings a new dimension to the study of cancer and the search for effective therapeutic modalities for this disease. Cancer and Metastasis Reviews provides a forum for critical review and discussion of these challenging developments. A major function of the journal is to review some of the more important and interesting recent developments in the biology and treatment of malignant disease, as well as to highlight new and promising directions, be they technological or conceptual. Contributors are encouraged to review their personal work and be speculative.