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Updated: Jun 6, 2026

Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Spry2 expression correlates with BRAF mutation in thyroid cancer
Lizhong Xu1, Jun Liang Zhou, Michael Cohen
1Department of Biochemistry, New York University Langone Medical Center, New York, NY, USA.
Background:
BRAF mutations activate the mitogen-activated protein kinase pathway and often confer an aggressive thyroid cancer (TC) phenotype. Spry2 is an inducible negative feedback regulator of the mitogen-activated protein kinase (MAPK) pathway. The aim of this study was to investigate the role of Spry2 in TC.
Methods:
TC cell lines were analyzed for Spry2 expression and MAPK pathway activation. Cells were treated with MEK inhibitor and Spry2 small hairpin RNA. Cells were analyzed for Spry2 expression and MEK/ERK phosphorylation (pMEK, pERK). Thirty human papillary TCs were analyzed for mitogen-activated protein kinase pathway activating mutations and Spry2 expression.
Results:
Increased baseline pMEK levels and Spry2 expression was found in BRAF V600E mutant (BRAF+) cells. MEK inhibition in BRAF+ cells showed decreased Spry2 expression and decreased pMEK/pERK levels. From our tissue samples, 10 papillary TCs had BRAF mutation, and increased Spry2 expression was found only in BRAF+ tumors.
Conclusion:
Spry2 expression correlates with BRAF status in vitro and in human tissue. Spry2 may serve as a negative feedback regulator of the mitogen-activated protein kinase pathway in BRAF+ TC. Increased Spry2 expression may serve as a surrogate marker of mitogen-activated protein kinase pathway activation with prognostic and therapeutic implications.
Insights
Spry2 expression correlates with BRAF mutations in thyroid cancer (TC). This suggests Spry2 may indicate mitogen-activated protein kinase pathway activation, potentially impacting prognosis and treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- BRAF mutations are linked to aggressive thyroid cancer (TC) by activating the MAPK pathway.
- Spry2 is a negative feedback regulator of the MAPK pathway.
Purpose of the Study:
- To investigate the role of Spry2 in thyroid cancer.
Main Methods:
- Analyzed Spry2 expression and MAPK pathway activation in TC cell lines.
- Treated cells with MEK inhibitor and Spry2 small hairpin RNA.
- Examined Spry2 expression and MAPK pathway mutations in human papillary TCs.
Main Results:
- BRAF V600E mutant (BRAF+) cells showed increased baseline pMEK and Spry2 expression.
- MEK inhibition in BRAF+ cells decreased Spry2 and pMEK/pERK levels.
- BRAF+ human papillary TCs exhibited increased Spry2 expression.
Conclusions:
- Spry2 expression correlates with BRAF status in vitro and in human tissues.
- Spry2 may act as a negative feedback regulator in BRAF+ TC.
- Increased Spry2 expression could be a marker for MAPK pathway activation with prognostic and therapeutic implications.
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