Interaction between CD9 and PI3K‑p85 activates the PI3K/AKT signaling pathway in B‑lineage acute lymphoblastic leukemia

Shi,Yi-Fen; Huang,Zi-Yang; Huang,Yi-Sha; Dong,Ru-Jiao; Xing,Chong-Yun; Yu,Kang; Leung,Kam Tong; Feng,Jian-Hua

doi:10.3892/or.2021.8091

Interaction between CD9 and PI3K‑p85 activates the PI3K/AKT signaling pathway in B‑lineage acute lymphoblastic leukemia

Authors:
- Yi-Fen Shi
- Zi-Yang Huang
- Yi-Sha Huang
- Ru-Jiao Dong
- Chong-Yun Xing
- Kang Yu
- Kam Tong Leung
- Jian-Hua Feng
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Affiliations: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Paediatrics, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR 999077, P.R. China
Published online on: May 26, 2021 https://doi.org/10.3892/or.2021.8091
Article Number: 140

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Abstract

Our previous study has shown that CD9 knockdown could suppress cell proliferation, adhesion, migration and invasion, and promote apoptosis and the cytotoxicity of chemotherapeutic drugs in the B‑lineage acute lymphoblastic leukemia (B‑ALL) cell line SUP‑B15. In this study, we further investigated the molecular mechanism underlying the effects of CD9 on leukemic cell progression and the efficacy of chemotherapeutic agents in B‑ALL cells. Using the CD9‑knockdown SUP‑B15 cells, we demonstrated that the silencing of the CD9 gene significantly reduced the expression of phosphorylated‑phosphatidylinositol‑3 kinase (p‑PI3K), phosphorylated‑protein kinase B (p‑AKT), P‑glycoprotein (P‑gp), multidrug resistance‑associated protein 1 (MRP1), breast cancer resistance protein (BCRP), matrix metalloproteinase 2 (MMP2) and phosphorylated‑focal adhesion kinase (p‑FAK). In addition, glutathione S‑transferase (GST) pull‑down assay showed the binding between CD9 and both PI3K‑p85α and PI3K‑p85β in vitro, while co‑immunoprecipitation assay showed the binding between CD9 and both PI3K‑p85α and PI3K‑p85β in vivo. Furthermore, the PI3K/AKT inhibitor LY294002 mirrored the effects of CD9 knockdown in SUP‑B15 cells. Taken together, these findings demonstrated that CD9 activates the PI3K/AKT signaling pathway through direct interaction with PI3K‑p85 in B‑ALL cells. Our data provide evidence for the inhibition of the PI3K/AKT pathway as a novel therapeutic option in CD9 antigen‑positive B‑ALL.

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