Lemur tyrosine kinase-3 (LMTK3) induces chemoresistance to cetuximab in colorectal cancer via the ERK/MAPK pathway
| Autor: | Yanjing Gu, Xi Gu, Miaomiao Yang, Cheng Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
MAPK/ERK pathway
Adult Male MAP Kinase Signaling System Cell Cetuximab Bioengineering colorectal cancer Apoptosis Protein Serine-Threonine Kinases Applied Microbiology and Biotechnology Flow cytometry resistance Antineoplastic Agents Immunological LMTK3 Cell Line Tumor medicine Humans Lemur tyrosine kinase 3 Viability assay ERK/MAPK medicine.diagnostic_test Kinase Chemistry Membrane Proteins General Medicine Cell cycle digestive system diseases medicine.anatomical_structure Drug Resistance Neoplasm Gene Knockdown Techniques Cancer research Female Colorectal Neoplasms TP248.13-248.65 Biotechnology Research Article Research Paper |
| Zdroj: | Bioengineered article-version (VoR) Version of Record Bioengineered, Vol 12, Iss 1, Pp 6594-6605 (2021) |
| ISSN: | 2165-5987 2165-5979 |
| Popis: | As an oncogenic kinase in multiple cancers, LMTK3 was deeply implicated in cancer pathogenesis. Nevertheless, its biological function in colorectal cancer (CRC) is still unclear. In this study, LMTK3 mRNA expression was assessed by RT-qPCR. LMTK3, phospho-ERK1/2 (p-ERK1/2), ERK1/2, and cleaved caspase-3 protein levels were detected by western blotting. Cetuximab (CTX)-resistant CRC cell models were constructed to investigate the mechanism of LMTK3-regulated CTX resistance in CRC. CTX half-maximal inhibitory concentration (IC50), viability, apoptosis, cell cycle, migration, and invasion of CRC cells were analyzed via Cell Counting Kit-8 (CCK-8), flow cytometry, wound healing, and transwell assays. We found LMTK3 was distinctly upregulated in CRC tissues and cells, particularly in CTX-resistant CRC tissues and cells. LMTK3 inhibition lowered CTX half-maximal inhibitory concentration (IC50) value, inhibited cell viability, induced cell apoptosis, triggered cell-cycle arrest, and impaired cell metastatic capability in CTX-resistant CRC cells. Moreover, we also demonstrated that LMTK3 induced CTX resistance in CRC via the activation of ERK/MAPK signaling in vitro. These results suggested a novel molecular mechanism by which LMTK3 participates in the development of CTX resistance in CRC. |
| Databáze: | OpenAIRE |
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