CD147-targeted siRNA in A375 malignant melanoma cells induces the phosphorylation of EGFR and downregulates cdc25C and MEK phosphorylation

Hatanaka,Miho; Higashi,Yuko; Kawai,Kazuhiro; Su,Juan; Zeng,Weiqi; Chen,Xiang; Kanekura,Takuro

doi:10.3892/ol.2016.4267

CD147-targeted siRNA in A375 malignant melanoma cells induces the phosphorylation of EGFR and downregulates cdc25C and MEK phosphorylation

Authors:
- Miho Hatanaka
- Yuko Higashi
- Kazuhiro Kawai
- Juan Su
- Weiqi Zeng
- Xiang Chen
- Takuro Kanekura
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Affiliations: Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8520, Japan, Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: February 24, 2016 https://doi.org/10.3892/ol.2016.4267
Pages: 2424-2428

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Abstract

The Raf-MEK-ERK signaling pathway is important during oncogenesis. An activating mutation of BRAF constitutively activates the Raf-MEK-ERK signaling cascade, and has been identified in ~70% of malignant melanomas (MMs). Cluster of differentiation 147 (CD147)/basigin is an integral plasma membrane protein belonging to the immunoglobulin superfamily. The protein is highly expressed on MM cells, and promotes cellular proliferation and tumor growth. The present study investigated the correlation between CD147 expression and Raf-MEK-ERK signaling in MM using the A375 human MM cell line, which harbors the activating mutation of BRAF. The phosphorylation of epidermal growth factor receptor (EGFR) was upregulated, and mitogen-activated protein kinase kinase (MEK) and cell division cycle 25C phosphorylation was downregulated by CD147 silencing in the A375 cells. Cell growth was inhibited by the EGFR inhibitor erlotinib and by CD147 silencing, and additive growth inhibition was observed when these techniques were combined. The results of the present study indicate that the combination of EGFR and CD147 inhibition may be useful in BRAF-mutated MM.

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