ECB-ART-50978
Oncol Lett
2022 Jun 24;242:277. doi: 10.3892/ol.2022.13397.
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EML4-ALK fusion gene in non-small cell lung cancer.
Lei Y
,
Lei Y
,
Shi X
,
Wang J
.
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Non-small cell lung cancer (NSCLC) is a malignant tumor with a high morbidity and mortality rate that is a threat to human health. With the development of molecular targeted research, breakthroughs have been made on the molecular mechanism of lung cancer. The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene is one of the most important pathogenic driver genes of NSCLC discovered thus far. Four generations of targeted drugs for EML4-ALK have been developed, with patients benefiting significantly from these drugs. Therefore, EML4-ALK has become a research hotspot in NSCLC. The aim of the present study is to introduce the current research progress of EML4-ALK and its association with NSCLC.
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Figure 1. Schematic diagram of the EML4-ALK fusion gene. During embryonic development, ligands activate ALK to form ALK dimers, which are involved in regulating the growth and development of the nervous system. When the EML4-ALK fusion gene is formed, it can be directly activated without the need for ligands, and abnormally activate downstream signaling pathways, promote cell proliferation and invasion, and inhibit apoptosis, ultimately leading to the occurrence of NSCLC. TD, trimerization domain; BD, basic domain; HELP, hydrophobic motif in EML proteins; WD, tryptophan-aspartic acid repeats; TM, transmembrane domain; NSCLC, non-small cell lung cancer; EML4, echinoderm microtubule-associated protein-like 4; ALK, anaplastic lymphoma kinase. |
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Figure 2. Three most important variants of EML4-ALK. EML4-ALK V1, EML4-ALK V2 and EML4-ALK V3 a/b are formed by inserting exon 13 (E13), exon 20 (E20) and exon 6 (E6) of EML4, respectively, into exon 20 (A20) of ALK. EML4, echinoderm microtubule-associated protein-like 4; ALK, anaplastic lymphoma kinase. |
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