ALCAM-EGFR interaction regulates myelomagenesis.
Hongmei LuoDan ZhangFangfang WangQiang WangYu WuMaling GouYiguo HuWenyan ZhangJingcao HuangYuping GongLing PanTianshu LiPan ZhaoDanfeng ZhangYing QuZhigang LiuTao JiangYang DaiTingting GuoJiang ZhuLingqun YeLi ZhangWeiping LiuQing YiYuhuan ZhengPublished in: Blood advances (2022)
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.
Keyphrases
- epidermal growth factor receptor
- tyrosine kinase
- multiple myeloma
- small cell lung cancer
- growth factor
- pi k akt
- newly diagnosed
- bone marrow
- cell cycle arrest
- advanced non small cell lung cancer
- single cell
- signaling pathway
- cell therapy
- induced apoptosis
- mesenchymal stem cells
- transcription factor
- poor prognosis
- gene expression
- cell death
- ejection fraction
- peripheral blood
- patient reported outcomes