Leucine-rich Repeat and Immunoglobulin Domain-containing Protein-1 (Lrig1) Negative Regulatory Action toward ErbB Receptor Tyrosine Kinases Is Opposed by Leucine-rich Repeat and Immunoglobulin Domain-containing Protein 3 (Lrig3)

Rafidi, Hanine; Mercado, Francisco García Gómez de; Astudillo, Michael; Fry, William; Saldana, Matthew; Carraway, Kermit L.; Sweeney, Colleen

doi:10.1074/jbc.m113.486050

Cited by 33 publications

(48 citation statements)

References 35 publications

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“…LRIG mutations with a high impact score according to Mutation Assessor are shown in in Table 1. High impact mutations are localized exclusively to the extracellular domain which is not unexpected given the conservation of this region of LRIGs and the requirement of the extracellular domain for recognition of interacting partners (Gur et al ., 2004, Rafidi et al ., 2013). …”

Section: Lrig Expression In Cancermentioning

confidence: 99%

“…Recently, deletion analysis of LRIG1 led to the finding that Δ-cyto LRIG1 (lacking the entire cytoplasmic domain which contains the c-Cbl binding site) is fully active in mediating ErbB2 degradation (Rafidi et al ., 2013), underscoring the existence of a c-Cbl independent mechanism for LRIG1. This is supported by the prior finding that Δ-cyto LRIG1 and wild type LRIG1 have similar abilities to inhibit the growth of glioma cells (Yi et al ., 2011).…”

Section: Lrig Mechanism Of Actionmentioning

confidence: 99%

“…Less is known regarding the specific molecular functions of LRIG2 and LRIG3 although they do not appear to have the same global ability to decrease growth factor receptor expression. LRIG2 has no significant effect on the expression of EGFR, ErbB2 (Rafidi et al , 2013) or PDGFRα/β (Rondahl et al , 2013) while LRIG3 has been found to oppose LRIG1 (Rafidi et al , 2013) and increase expression of ErbBs 1-4 (Rafidi et al , 2013). LRIG1 limits LRIG3 action by promoting its proteolytic degradation, highlighting a complex cross-talk amongst LRIG family members (Rafidi et al ., 2013).…”

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

The LRIG family: enigmatic regulators of growth factor receptor signaling

Simion¹,

Cedano-Prieto²,

Sweeney³

2014

Endocrine-Related Cancer

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The LRIG (leucine-rich repeats and immunoglobulin-like domains) family of transmembrane proteins contains three vertebrate members (LRIG1, LRIG2, LRIG3) and one member each in flies (Lambik) and worms (Sma-10). LRIGs have stepped into the spotlight as essential regulators of growth factor receptors, including receptor tyrosine and serine/threonine kinases. LRIGs have been found to both negatively (LRIG1, LRIG3) and positively (Sma-10, LRIG3) regulate growth factor receptor expression and signaling, although the precise molecular mechanisms by which LRIGs function are not yet understood. The most is known about LRIG1, which was recently demonstrated to be a tumor suppressor. Indeed, in vivo experiments reinforce the essential link between LRIG1 and repression of its targets for tissue homeostasis. LRIG1 has also been identified as a stem cell marker and regulator of stem cell quiescence in a variety of tissues, discussed within. Comparably less is known about LRIG2 and LRIG3 although studies to date suggest that their functions are largely distinct from LRIG1 and that they likely do not serve as growth/tumor suppressors. Finally, the translational applications of expressing soluble forms of LRIG1 in LRIG1-deficient tumors are being explored and hold tremendous promise.

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Section: Lrig Expression In Cancermentioning

confidence: 99%

Section: Lrig Mechanism Of Actionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

The LRIG family: enigmatic regulators of growth factor receptor signaling

Simion¹,

Cedano-Prieto²,

Sweeney³

2014

Endocrine-Related Cancer

Self Cite

View full text Add to dashboard Cite

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“…Note Recently, Colleen Sweeney and Lisa V Goodrich reported that overexpression of LRIG3 in HEK293T cells increased the ERBB receptor expression (Rafidi et al, 2013). However, downregulation of LRIG3 in a human glioblastoma cell line, GL15, resulted in upregulation of total EGFR and phospho-EGFR, and enchanced glioma cell proliferation, adhesion and invasion .…”

Section: To Be Notedmentioning

confidence: 99%

LRIG3 (Leucine-Rich Repeats And Immunoglobulin-Like Domains 3)

Guo¹,

Mao²,

Lei³

2015

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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LRIG3 is a member of mammalian LRIG family and less is known about the functions of LRIG3. Accumulating evidences showed that LRIG3 may also function as a tumor suppressor like LRIG1. LRIG3 can inhibit tumor cell proliferation, survival, adhesion and invasion in many types of human cancer cells based on cell experiments. Perinuclear staining of LRIG3 correlated with better survival in astrocytic tumors. Decreased LRIG3 was identified as one of 12 promising serum biomarkers for early stage non-small-cell lung cancer. LRIG3 may play a role in inner ear morphogenesis and neural crest formation.

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“…The gene LRIG1 (leucine-rich repeat and immunoglobulin domain-containing protein-1) has been found to be a tumor suppressor gene (Rafidi et al, 2013). Research has shown that the mRNA and protein expression of this gene were reduced in a variety of tumor cells, including pituitary tumor cell lines and pituitary tumor tissue, compared with normal tissue.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of subcutaneously implanted human pituitary tumor cells in nude mice by LRIG1

Wang

et al. 2016

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to explore the inhibition of subcutaneously implanted human pituitary tumor cells in nude mice by LRIG1 and its mechanism. For this study, athymic nude mice were injected with either normal pituitary tumor RC-4B/C cells or LRIG1-transfected RC-4B/C cells. We then calculated the volume inhibition rate of the tumors, as well as the apoptosis index of tumor cells and the expression of Ras, Raf, AKt, and ERK mRNA in tumor cells. Tumor cell morphological and structural changes were also observed under electron microscope. Our data showed that subcutaneous tumor growth was slowed or even halted in LRIG1-transfected tumors. The tumor volumes were significantly different between the two groups of mice (c 2 = 2.14, P < 0.05). The tumor apoptosis index was found to be 8.72% in the control group and 39.7% in LRIG1-transfected mice (c 2 = 7.59, P < 0.05). The levels of Ras, Raf, and AKt mRNA in LRIG1-transfected RC-4B/C cells were significantly reduced after transfection (P < 0.01). Transfected subcutaneous tumor cells appeared to be in early or late apoptosis under an electron microscope, while only a few subcutaneous tumor cells appeared to be undergoing apoptosis in the control group. In conclusion, the LRIG1 gene is able to inhibit proliferation and promote apoptosis in subcutaneously implanted human pituitary tumors in nude mice. The mechanism of LRIG1 may involve the inhibition of the PI3K/ Akt and Ras/Raf/ERK signal transduction pathways.

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Leucine-rich Repeat and Immunoglobulin Domain-containing Protein-1 (Lrig1) Negative Regulatory Action toward ErbB Receptor Tyrosine Kinases Is Opposed by Leucine-rich Repeat and Immunoglobulin Domain-containing Protein 3 (Lrig3)

Cited by 33 publications

References 35 publications

The LRIG family: enigmatic regulators of growth factor receptor signaling

The LRIG family: enigmatic regulators of growth factor receptor signaling

LRIG3 (Leucine-Rich Repeats And Immunoglobulin-Like Domains 3)

Inhibition of subcutaneously implanted human pituitary tumor cells in nude mice by LRIG1

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