Tianchi Xin, Sara Gallini, Haoyang Wei, David G. Gonzalez, Catherine Matte-Martone, Hiroki Machida, Hironobu Fujiwara, H. Amalia Pasolli, Kathleen C. Suozzi, Lauren E. Gonzalez, Sergi Regot, Valentina Greco
{"title":"致癌 Kras 通过将脉冲式 ERK 激活转化为持续式 ERK 激活,诱导时空特异性组织变形","authors":"Tianchi Xin, Sara Gallini, Haoyang Wei, David G. Gonzalez, Catherine Matte-Martone, Hiroki Machida, Hironobu Fujiwara, H. Amalia Pasolli, Kathleen C. Suozzi, Lauren E. Gonzalez, Sergi Regot, Valentina Greco","doi":"10.1038/s41556-024-01413-y","DOIUrl":null,"url":null,"abstract":"Tissue regeneration and maintenance rely on coordinated stem cell behaviours. This orchestration can be impaired by oncogenic mutations leading to cancer. However, it is largely unclear how oncogenes perturb stem cells’ orchestration to disrupt tissue. Here we used intravital imaging to investigate the mechanisms by which oncogenic Kras mutation causes tissue disruption in the hair follicle. Through longitudinally tracking hair follicles in live mice, we found that KrasG12D, a mutation that can lead to squamous cell carcinoma, induces epithelial tissue deformation in a spatiotemporally specific manner, linked with abnormal cell division and migration. Using a reporter mouse capture real-time ERK signal dynamics at the single-cell level, we discovered that KrasG12D, but not a closely related mutation HrasG12V, converts ERK signal in stem cells from pulsatile to sustained. Finally, we demonstrated that interrupting sustained ERK signal reverts KrasG12D-induced tissue deformation through modulating specific features of cell migration and division. Xin et al. show, through intravital imaging, that KrasG12D induces epithelial tissue deformation in a spatiotemporally specific manner by converting the pulsatile ERK signal fluctuation in stem cells into sustained activation.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":17.3000,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Oncogenic Kras induces spatiotemporally specific tissue deformation through converting pulsatile into sustained ERK activation\",\"authors\":\"Tianchi Xin, Sara Gallini, Haoyang Wei, David G. Gonzalez, Catherine Matte-Martone, Hiroki Machida, Hironobu Fujiwara, H. Amalia Pasolli, Kathleen C. Suozzi, Lauren E. Gonzalez, Sergi Regot, Valentina Greco\",\"doi\":\"10.1038/s41556-024-01413-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Tissue regeneration and maintenance rely on coordinated stem cell behaviours. This orchestration can be impaired by oncogenic mutations leading to cancer. However, it is largely unclear how oncogenes perturb stem cells’ orchestration to disrupt tissue. Here we used intravital imaging to investigate the mechanisms by which oncogenic Kras mutation causes tissue disruption in the hair follicle. Through longitudinally tracking hair follicles in live mice, we found that KrasG12D, a mutation that can lead to squamous cell carcinoma, induces epithelial tissue deformation in a spatiotemporally specific manner, linked with abnormal cell division and migration. Using a reporter mouse capture real-time ERK signal dynamics at the single-cell level, we discovered that KrasG12D, but not a closely related mutation HrasG12V, converts ERK signal in stem cells from pulsatile to sustained. Finally, we demonstrated that interrupting sustained ERK signal reverts KrasG12D-induced tissue deformation through modulating specific features of cell migration and division. Xin et al. show, through intravital imaging, that KrasG12D induces epithelial tissue deformation in a spatiotemporally specific manner by converting the pulsatile ERK signal fluctuation in stem cells into sustained activation.\",\"PeriodicalId\":18977,\"journal\":{\"name\":\"Nature Cell Biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":17.3000,\"publicationDate\":\"2024-04-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Cell Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.nature.com/articles/s41556-024-01413-y\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Cell Biology","FirstCategoryId":"99","ListUrlMain":"https://www.nature.com/articles/s41556-024-01413-y","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Oncogenic Kras induces spatiotemporally specific tissue deformation through converting pulsatile into sustained ERK activation
Tissue regeneration and maintenance rely on coordinated stem cell behaviours. This orchestration can be impaired by oncogenic mutations leading to cancer. However, it is largely unclear how oncogenes perturb stem cells’ orchestration to disrupt tissue. Here we used intravital imaging to investigate the mechanisms by which oncogenic Kras mutation causes tissue disruption in the hair follicle. Through longitudinally tracking hair follicles in live mice, we found that KrasG12D, a mutation that can lead to squamous cell carcinoma, induces epithelial tissue deformation in a spatiotemporally specific manner, linked with abnormal cell division and migration. Using a reporter mouse capture real-time ERK signal dynamics at the single-cell level, we discovered that KrasG12D, but not a closely related mutation HrasG12V, converts ERK signal in stem cells from pulsatile to sustained. Finally, we demonstrated that interrupting sustained ERK signal reverts KrasG12D-induced tissue deformation through modulating specific features of cell migration and division. Xin et al. show, through intravital imaging, that KrasG12D induces epithelial tissue deformation in a spatiotemporally specific manner by converting the pulsatile ERK signal fluctuation in stem cells into sustained activation.
期刊介绍:
Nature Cell Biology, a prestigious journal, upholds a commitment to publishing papers of the highest quality across all areas of cell biology, with a particular focus on elucidating mechanisms underlying fundamental cell biological processes. The journal's broad scope encompasses various areas of interest, including but not limited to:
-Autophagy
-Cancer biology
-Cell adhesion and migration
-Cell cycle and growth
-Cell death
-Chromatin and epigenetics
-Cytoskeletal dynamics
-Developmental biology
-DNA replication and repair
-Mechanisms of human disease
-Mechanobiology
-Membrane traffic and dynamics
-Metabolism
-Nuclear organization and dynamics
-Organelle biology
-Proteolysis and quality control
-RNA biology
-Signal transduction
-Stem cell biology