LMTK3 knockdown retards cell growth and invasion and promotes apoptosis in thyroid cancer

Abstract

Lemur tyrosine kinase-3 (LMTK3) is a member of the serine/threonine tyrosine kinase family, which is thought to be involved in tumor progression and prognosis. The purpose of the present study was to determine the diagnostic significance and therapeutic targets in thyroid cancer. ELISA assay was used to detect the protein expression of serum LMTK3. Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction were employed to measure the expression of LMTK3. Flow cytometry was used to determine the cell cycle. Transwell assay was used to measure the invasion and migration of SW579 cells and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay to detect cell apoptosis. The LMTK3 level was positively associated with disease stage and pathological type, whereas there was no correlation between LMTK3 level and gender, age, tumor size or lymph node metastasis. The serum LMTK3 level was significantly increased in 102 thyroid carcinoma patients compared with 52 benign thyroid tumor patients and 50 healthy volunteers (P=0.001). The protein and mRNA expression of LMTK3 was markedly higher in thyroid cancer patients compared with patients with benign thyroid tumors. Notably, LMTK3 knockdown retarded proliferation, invasion and migration in SW579 cells. In addition, downregulation of LMTK3 promoted apoptosis in SW579 cells. These findings indicated that LMTK3 knockdown retards the growth of thyroid cancer cells partly through inhibiting proliferation, invasion, migration and inducing apoptosis in SW579 cells. It may serve as a useful diagnostic biomarker and a novel therapeutic target for patients with thyroid cancer.

The structure-function relationship of oncogenic LMTK3

“…LMTK3 has been reported to be involved in several cancer types (5,7,11,(14)(15)(16). However, the lack of crystal structure has impeded an understanding of the role of this protein and its interactions with other molecules.…”

“…S3C). We also pinpointed Ser 15 and Ser 82 as the main HSP27 residues phosphorylated by LMTK3 in vitro, using site-directed mutagenesis ( fig. S3D), while both sites were in accordance with the identified LMTK3 phospho-motif.…”

LMTK3 promotes tumorigenesis in bladder cancer via the ERK/MAPK pathway

“…Further studies clarified that LMTK3 may regulate these biological functions by the ERK/MAPK signaling pathway. Emerging evidence showed that LMTK3 played a pivotal role in the tumorigenesis and progression of most cancers [2][3][4]. In 2011, Giamas et al [8] identified LMTK3 as a therapeutic target in breast cancer.…”

“…indirectly participate in a variety of cell signaling pathway transductions, such as estrogen receptor pathway, Wnt signaling pathway and forkhead box O3 pathway, among others. Previous research found that LMTK3 is highly expressed in many malignant tumors; its high expression is significantly correlated with the oncogenesis, progression and prognosis of various tumors [2][3][4]. Zhang et al [5] found that LMTK3 is a novel biomarker for primary non-small cell lung cancer, and high expression of LMTK3 predicts unfavorable clinical prognosis.…”

Endocrine Resistance in Hormone Receptor Positive Breast Cancer–From Mechanism to Therapy

“…Lemur tyrosine kinase 3 (LMTK3) is a serine-threonine-tyrosine protein kinase involved in various cancers. Aberrant expression of the gene and polymorphisms within the gene serve as suitable biomarkers in cancer progression (350, 351). LMTK3 is expressed in both ER+ and ER-negative BCs and a kinome screen identified it as an ERα regulator (352).…”