Simmons Jacinta L, Neuendorf Hannah M, Boyle Glen M
Cancer Drug Mechanisms Group, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia.
School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Qld, Australia.
Exp Dermatol. 2022 Jan;31(1):89-93. doi: 10.1111/exd.14225. Epub 2020 Nov 20.
The inverse relationship between transcription factor MITF and receptor tyrosine kinase AXL has received much attention recently. It is thought that melanoma tumors showing AXL /MITF levels are resistant to therapy. We show here that a population of cells within melanoma tumors with extremely high expression of AXL are negative/low for both MITF and the transcription factor BRN2. Depletion of both transcription factors from cultured melanoma cell lines produced an increase in AXL expression greater than depletion of MITF alone. Further, re-expression of BRN2 led to decreased AXL expression, indicating a role for BRN2 in regulation of AXL levels unrelated to effects on MITF level. As AXL has been recognized as a marker of therapy resistance, these cells may represent a population of cells responsible for disease relapse and as potential targets for therapeutic treatment.
转录因子MITF与受体酪氨酸激酶AXL之间的负相关关系近来备受关注。据认为，AXL/MITF水平呈阳性的黑色素瘤肿瘤对治疗具有抗性。我们在此表明，黑色素瘤肿瘤内AXL表达极高的一群细胞，其MITF和转录因子BRN2均呈阴性/低表达。从培养的黑色素瘤细胞系中耗尽这两种转录因子，导致AXL表达的增加幅度大于仅耗尽MITF时的情况。此外，BRN2的重新表达导致AXL表达降低，表明BRN2在AXL水平调控中发挥作用，且这种作用与对MITF水平的影响无关。由于AXL已被视为治疗抗性的标志物，这些细胞可能代表了一群导致疾病复发的细胞，并且是治疗的潜在靶点。
