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LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer

  • Authors:
    • David Lindquist
    • Fernando C. Alsina
    • Carl Herdenberg
    • Catharina Larsson
    • Jo Höppener
    • Na Wang
    • Gustavo Paratcha
    • Miklós Tarján
    • Tibor Tot
    • Roger Henriksson
    • Håkan Hedman
  • View Affiliations / Copyright

    Affiliations: Oncology Research Laboratory, Department of Radiation Sciences, Umeå University, SE-90187 Umeå, Sweden, Institute of Cell Biology and Neuroscience (IBCN)-CONICET, School of Medicine, University of Buenos Aires (UBA), Buenos Aires 1121, Argentina, Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden, University Medical Center Utrecht, Division of Biomedical Genetics and Laboratory of Translational Immunology, 3508 GA Utrecht, The Netherlands, Department of Pathology and Clinical Cytology, Central Hospital Falun, 791 82 Falun, Sweden
    Copyright: © Lindquist et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1189-1197
    |
    Published online on: February 9, 2018
       https://doi.org/10.3892/ijo.2018.4273
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Abstract

Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) are characterized by genomic rearrangements and point mutations in the proto-oncogene RET. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a suppressor of various receptor tyrosine kinases, including RET. LRIG1 expression levels are associated with patient survival in many cancer types. In the present study, we investigated whether the oncogenic RET mutants RET2A (C634R) and RET2B (M918T) were regulated by LRIG1, and the possible effects of LRIG1 expression in thyroid cancer were investigated in three different clinical cohorts and in a RET2B-driven mouse model of MTC. LRIG1 was shown to physically interact with both RET2A and RET2B and to restrict their ligand-independent activation. LRIG1 mRNA levels were downregulated in PTC and MTC compared to normal thyroid gland tissue. There was no apparent association between LRIG1 RNA or protein expression levels and patient survival in the studied cohorts. The transgenic RET2B mice developed pre-cancerous medullary thyroid lesions at a high frequency (36%); however, no overt cancers were observed. There was no significant difference in the incidence of pre-cancerous lesions between Lrig1 wild-type and Lrig1-deficient RET2B mice. In conclusion, the findings that LRIG1 is a negative regulator of RET2A and RET2B and is also downregulated in PTC and MTC may suggest that LRIG1 functions as a thyroid tumor suppressor.
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Copy and paste a formatted citation
Spandidos Publications style
Lindquist D, Alsina FC, Herdenberg C, Larsson C, Höppener J, Wang N, Paratcha G, Tarján M, Tot T, Henriksson R, Henriksson R, et al: LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer. Int J Oncol 52: 1189-1197, 2018.
APA
Lindquist, D., Alsina, F.C., Herdenberg, C., Larsson, C., Höppener, J., Wang, N. ... Hedman, H. (2018). LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer. International Journal of Oncology, 52, 1189-1197. https://doi.org/10.3892/ijo.2018.4273
MLA
Lindquist, D., Alsina, F. C., Herdenberg, C., Larsson, C., Höppener, J., Wang, N., Paratcha, G., Tarján, M., Tot, T., Henriksson, R., Hedman, H."LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer". International Journal of Oncology 52.4 (2018): 1189-1197.
Chicago
Lindquist, D., Alsina, F. C., Herdenberg, C., Larsson, C., Höppener, J., Wang, N., Paratcha, G., Tarján, M., Tot, T., Henriksson, R., Hedman, H."LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer". International Journal of Oncology 52, no. 4 (2018): 1189-1197. https://doi.org/10.3892/ijo.2018.4273
Copy and paste a formatted citation
x
Spandidos Publications style
Lindquist D, Alsina FC, Herdenberg C, Larsson C, Höppener J, Wang N, Paratcha G, Tarján M, Tot T, Henriksson R, Henriksson R, et al: LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer. Int J Oncol 52: 1189-1197, 2018.
APA
Lindquist, D., Alsina, F.C., Herdenberg, C., Larsson, C., Höppener, J., Wang, N. ... Hedman, H. (2018). LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer. International Journal of Oncology, 52, 1189-1197. https://doi.org/10.3892/ijo.2018.4273
MLA
Lindquist, D., Alsina, F. C., Herdenberg, C., Larsson, C., Höppener, J., Wang, N., Paratcha, G., Tarján, M., Tot, T., Henriksson, R., Hedman, H."LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer". International Journal of Oncology 52.4 (2018): 1189-1197.
Chicago
Lindquist, D., Alsina, F. C., Herdenberg, C., Larsson, C., Höppener, J., Wang, N., Paratcha, G., Tarján, M., Tot, T., Henriksson, R., Hedman, H."LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer". International Journal of Oncology 52, no. 4 (2018): 1189-1197. https://doi.org/10.3892/ijo.2018.4273
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