ArticleCancer research2012
LRIG1 modulates cancer cell sensitivity to Smac mimetics by regulating TNFα expression and receptor tyrosine kinase signaling.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Midostaurin response in AML is shaped by a progenitor-like cell state selectively targeted by SMAC mimetics.NPJ precision oncology · 2026Article
- HPV8-induced STAT3 activation led keratinocyte stem cell expansion in human actinic keratoses.JCI insight · 2024Article
- Review
- Review
- LRIG1 is a pleiotropic androgen receptor-regulated feedback tumor suppressor in prostate cancer.Nature communications · 2019Article
- SM‑164 enhances the antitumor activity of adriamycin in human U2‑OS cells via downregulation of X‑linked inhibitor of apoptosis protein.Molecular medicine reports · 2019Article
- cIAP1 regulates the EGFR/Snai2 axis in triple-negative breast cancer cells.Cell death and differentiation · 2018Article
- Derivatization of inhibitor of apoptosis protein (IAP) ligands yields improved inducers of estrogen receptor α degradation.The Journal of biological chemistry · 2018Article
- Downregulation of leucine-rich repeats and immunoglobulin-like domains 1 by microRNA-20a modulates gastric cancer multidrug resistance.Cancer science · 2018Article
- Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF-A pathway.Oncology letters · 2017Article
- LCL161 increases paclitaxel-induced apoptosis by degrading cIAP1 and cIAP2 in NSCLC.Journal of experimental & clinical cancer research : CR · 2016Article
- LRIG1 opposes epithelial-to-mesenchymal transition and inhibits invasion of basal-like breast cancer cells.Oncogene · 2016Article
- PKC activation sensitizes basal-like breast cancer cell lines to Smac mimetics.Cell death discovery · 2016Article
- USP11-dependent selective cIAP2 deubiquitylation and stabilization determine sensitivity to Smac mimetics.Cell death and differentiation · 2015Article
- LRIG1 enhances the radiosensitivity of radioresistant human glioblastoma U251 cells via attenuation of the EGFR/Akt signaling pathway.International journal of clinical and experimental pathology · 2015Article
- Small-molecule SMAC mimetics as new cancer therapeutics.Pharmacology & therapeutics · 2014Review
- LRIG and cancer prognosis.Acta oncologica (Stockholm, Sweden) · 2014Review
- The LRIG family: enigmatic regulators of growth factor receptor signaling.Endocrine-related cancer · 2014Review
- BM-1197: a novel and specific Bcl-2/Bcl-xL inhibitor inducing complete and long-lasting tumor regression in vivo.PloS one · 2014Article
- Identification of DR5 as a critical, NF-κB-regulated mediator of Smac-induced apoptosis.Cell death & disease · 2013Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Smac mimetics block inhibitor of apoptosis proteins to trigger TNFα-dependent apoptosis in cancer cells. However, only a small subset of cancer cells seem to be sensitive to Smac mimetics and even sensitive cells can develop resistance. Herein, we elucidated mechanisms underlying the intrinsic and acquired resistance of cancer cells to Smac mimetics. In vitro and in vivo investigations revealed that the expression of the cell surface protein LRIG1, a negative regulator of receptor tyrosine kinases (RTK), is downregulated in resistant derivatives of breast cancer cells sensitive to Smac mimetics. RNA interference-mediated downregulation of LRIG1 markedly attenuated the growth inhibitory activity of the Smac mimetic SM-164 in drug-sensitive breast and ovarian cancer cells. Furthermore, LRIG1 downregulation attenuated TNFα gene expression induced by Smac mimetics and increased the activity of multiple RTKs, including c-Met and Ron. The multitargeted tyrosine kinase inhibitors Crizotinib and GSK1363089 greatly enhanced the anticancer activity of SM-164 in all resistant cell derivatives, with the combination of SM-164 and GSK1363089 also completely inhibiting the outgrowth of resistant tumors in vivo. Together, our findings show that both upregulation of RTK signaling and attenuated TNFα expression caused by LRIG1 downregulation confers resistance to Smac mimetics, with implications for a rational combination strategy.
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Registered trials
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.