Neurotrophin Receptors TrkA, p75(NTR), and Sortilin Are Increased and Targetable in Thyroid Cancer
authors Faulkner, S; Jobling, P; Rowe, CW; Oliveira, SMR; Roselli, S; Thorne, RF; Oldmeadow, C; Attia, J; Jiang, CC; Zhang, XD; Walker, MM; Hondermarck, H
nationality International
journal AMERICAN JOURNAL OF PATHOLOGY
keywords NERVE GROWTH-FACTOR; BREAST-CANCER; PANCREATIC-CANCER; CELLS; INVASION; PROGRESSION; KINASE; PAIN; PROLIFERATION; EXPRESSION
abstract Neurotrophin receptors are emerging targets in oncology, but their clinicopathologic significance in thyroid cancer is unclear. In this study, the neurotrophin tyrosine receptor kinase TrkA (also called NTRK1), the common neurotrophin receptor p75(NTR), and the proneurotrophin receptor sortilin were analyzed with immunohistochemistry in a cohort of thyroid cancers (n = 128) and compared with adenomas and normal thyroid tissues (n = 62). TrkA was detected in 20% of thyroid cancers, compared with none of the benign samples (P = 0.0007). TrkA expression was independent of histologic subtypes but associated with lymph node metastasis (P = 0.0148), suggesting the involvement of TrkA in tumor invasiveness. Nerves in the tumor microenvironment were positive for TrkA. p75(NTR) was overexpressed in anaplastic thyroid cancers compared with papillary and follicular subtypes (P < 0.0001). Sortilin was overexpressed in thyroid cancers compared with benign thyroid tissues (P < 0.0001). Neurotrophin receptor expression was confirmed in a panel of thyroid cancer cell lines at the mRNA and protein levels. Functional investigations using the anaplastic thyroid cancer cell line CAL-62 found that siRNA against TrkA, p75(NTR), and sortilin decreased cell survival and cell migration through decreased SRC and ERK activation. Together, these data reveal TrkA, p75(NTR), and sortilin as potential therapeutic targets in thyroid cancer.
publisher ELSEVIER SCIENCE INC
issn 0002-9440
year published 2018
volume 188
issue 1
beginning page 229
ending page 241
digital object identifier (doi) 10.1016/j.ajpath.2017.09.008
web of science category Pathology
subject category Pathology
unique article identifier WOS:000418634100023
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journal impact factor 4.069
5 year journal impact factor 4.583
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