ArticleNature medicine2012
LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 273 papers, 1 of them a synthesis that pooled it.
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Who cites it
273 citing papers in PubMed, 1 synthesis or guideline pooled it, 421 citations in OpenAlex.
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- Advancements of anticancer agents by targeting the Hippo signalling pathway: biological activity, selectivity, docking analysis, and structure-activity relationship.Molecular diversity · 2025Review
- YAP controls cell migration and invasion through a Rho GTPase switch.Science signaling · 2025Article
- The Roles of STAT3 and STAT5 in Breast Cancer.Cancers · 2025Review
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- Unraveling the Mystery of Breast Cancer Dormancy: Insights into Genetic, Receptor, and Cellular Interactions Driving Late Recurrence.Frontiers in immunology · 2025Review
- Investigating the role of transforming growth factor-beta/transforming growth factor-beta receptor in the development of hepatocellular carcinoma through the Salvador-Warts-Hippo pathway.International journal of molecular and cellular medicine · 2025Article
- Inhibition of microRNA-660-5p decreases breast cancer progression through direct targeting of TMEM41B.Hereditas · 2024Article
- Leukemia inhibitory factor (LIF) receptor amplifies pathogenic activation of fibroblasts in lung fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
213 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
There is a pressing need to identify prognostic markers of metastatic disease and targets for treatment. Combining high-throughput RNA sequencing, functional characterization, mechanistic studies and clinical validation, we identify leukemia inhibitory factor receptor (LIFR) as a breast cancer metastasis suppressor downstream of the microRNA miR-9 and upstream of Hippo signaling. Restoring LIFR expression in highly malignant tumor cells suppresses metastasis by triggering a Hippo kinase cascade that leads to phosphorylation, cytoplasmic retention and functional inactivation of the transcriptional coactivator YES-associated protein (YAP). Conversely, loss of LIFR in nonmetastatic breast cancer cells induces migration, invasion and metastatic colonization through activation of YAP. LIFR is downregulated in human breast carcinomas and inversely correlates with metastasis. Notably, in approximately 1,000 nonmetastatic breast tumors, LIFR expression status correlated with metastasis-free, recurrence-free and overall survival outcomes in the patients. These findings identify LIFR as a metastasis suppressor that functions through the Hippo-YAP pathway and has significant prognostic power.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.