LAUSR

NELL‐1 is a secreted protein that was originally found to be upregulated in pathologically fusing and fused sutures in non‐syndromic unilateral coronal synostosis patients. Apart from the ability of NELL‐1 to promote osteogenesis in long and craniofacial bones, NELL‐1 reportedly inhibits the formation of several benign and malignant tumors. We previously identified a novel transcript of Nell‐1 that lacked a calcium‐binding epidermal growth factor (EGF)‐like domain compared with full‐length Nell‐1; this new transcript was named Nell‐1‐ΔE. Three obvious structural differences between these two isoforms were revealed by homology modeling. Furthermore, the recombinant Nell‐1‐ΔE protein, but not the full‐length Nell‐1 protein, inhibited cell migration in vitro. However, full‐length Nell‐1 and Nell‐1‐ΔE proteins were present in similar subcellular locations and displayed similar expression patterns in both the intracellular and extracellular spaces. The results from the co‐immunoprecipitation and liquid chromatography/tandem mass spectrometry analyses using two cell lines demonstrated that Nell‐1‐ΔE but not full‐length Nell‐1 interacted with enolase‐1 in the extracellular spaces of both cell lines. The results of wound healing assays using ENO‐1‐overexpressing cells treated with full‐length Nell‐1/Nell‐1‐ΔE suggested that Nell‐1‐ΔE inhibited cell migration by interacting with ENO‐1. Our study indicated that the novel transcript Nell‐1‐ΔE, but not full‐length Nell‐1, might be a candidate tumor suppressor factor for basic research and clinical practice.