ETV6 Regulates Hemin-Induced Erythroid Differentiation of K562 Cells through Mediating the Raf/MEK/ERK Pathway

• Published in: Biological & pharmaceutical bulletin Vol. 45; no. 3; pp. 250 - 259
• Main Authors: Li, Zhaopeng, Sun, Ming-Zhong, Lv, Xinxin, Guo, Chunmei, Liu, Shuqing
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.03.2022; Japan Science and Technology Agency
• Subjects: Cell Differentiation; Cell proliferation; Chronic myeloid leukemia; E-Twenty Six variant 6; Embryogenesis; erythroid differentiation; ETS protein; ETS Translocation Variant 6 Protein; extracellular regulated protein kinase (ERK) pathway; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Fibrosarcoma; Hemin; Hemin - pharmacology; Hemoglobin; Humans; K562 Cells; Kinases; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; MAP Kinase Signaling System; Metabolic pathways; mitogen activated extracellular signal-regulated kinase (MEK); Mitogen-Activated Protein Kinase Kinases - metabolism; Myeloid leukemia; Protein kinase; Proto-Oncogene Proteins c-ets - metabolism; raf Kinases - metabolism; Raf protein; rapidly accelerated fibrosarcoma (Raf); Repressor Proteins - metabolism; Therapeutic targets; chronic myeloid leukemia; extracellular regulated protein kinase (ERK) pathway; mitogen activated extracellular signal-regulated kinase (MEK); rapidly accelerated fibrosarcoma (Raf); E-Twenty Six variant 6; erythroid differentiation
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b21-00632

As a member of transcription factor E-Twenty Six (ETS) family, ETS variant 6 (ETV6) plays significant role in hematopoiesis and embryonic development. ETV6 dysexpression also involved in the occurrence, development and progression of cancers and leukemia. In current work, we hypothesized that ETV6 plays a role in erythroid differentiation of chronic myeloid leukemia (CML). We found the protein expression level of ETV6 was significantly upregulated during hemin-induced erythroid differentiation of K562 cells. Moreover, overexpression of ETV6 inhibited erythroid differentiation in hemin-induced K562 cells with decreased numbers of benzidine-positive cells and decreased expression levels of erythroid differentiation specific markers glycophorin (GPA), CD71, hemoglobin A (HBA), α-globin, γ-globin and ε-globin. Conversely, ETV6 knockdown promoted erythroid differentiation in hemin-induced K562 cells. Furthermore, ETV6 expression level slightly positively with the proliferation capacity of K562 cells treated with hemin. Mechanistically, ETV6 overexpression inhibited fibrosarcoma/mitogen activated extracellular signal-regulated kinase/extracellular regulated protein kinase (Raf/MEK/ERK) pathway, ETV6 knockdown activated the Raf/MEK/ERK pathway. Collectively, the current work demonstrates that ETV6 plays an inhibitory role in the regulation of K562 cell erythroid differentiation via Raf/MEK/ERK pathway, it would be a potentially therapeutic target for dyserythropoiesis.