ALCAM-EGFR interaction regulates myelomagenesis

Hongmei Luo, Dan Zhang, Fangfang Wang, Qiang Wang, Yu Wu, Maling Gou, Yiguo Hu, Wenyan Zhang, Jingcao Huang, Yuping Gong, Ling Pan, Tianshu Li, Pan Zhao, Danfeng Zhang, Ying Qu, Zhigang Liu, Tao Jiang, Yang Dai, Tingting Guo, Jiang ZhuLingqun Ye, Li Zhang, Weiping Liu, Qing Yi, Yuhuan Zheng

Research output: Contribution to journalArticlepeer-review

Abstract

Multiple myeloma, a plasma cell malignancy in the bone marrow, remains largely incurable with currently available therapeutics. In this study, we discovered that the activated leukocyte cell adhesion molecule (ALCAM) interacted with epidermal growth factor receptor (EGFR), and regulated myelomagenesis. ALCAM was a negative regulator of myeloma clonogenicity. ALCAM expression was positively correlated with patients’ survival. ALCAM-knockdown myeloma cells displayed enhanced colony formation in the presence of bone marrow stromal cells (BMSCs). BMSCs supported myeloma colony formation by secreted epidermal growth factor (EGF), which bound with its receptor (EGFR) on myeloma cells and activated Mek/Erk cell signaling, PI3K/Akt cell signaling, and hedgehog pathway. ALCAM could also bind with EGFR, block EGF from binding to EGFR, and abolish EGFR-initiated cell signaling. Hence, our study identifies ALCAM as a novel negative regulator of myeloma pathogenesis.
Original languageUndefined/Unknown
Pages (from-to)5269-5282
Number of pages14
JournalBlood Advances
Volume5
Issue number23
DOIs
StatePublished - Dec 1 2021

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