J Cancer 2020; 11(6):1486-1494. doi:10.7150/jca.36189

Research Paper

LRG1 Suppresses Migration and Invasion of Esophageal Squamous Cell Carcinoma by Modulating Epithelial to Mesenchymal Transition

Ninggang Zhang1,2, Yaqiong Ren2, Yusheng Wang2, Lei Zhao1, Bin Wang1, Nina Ma1, Zhengxing Gao1, Bangwei Cao1✉

1. Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
2. Shanxi Cancer Hospital Affiliated to Shanxi Medical University, No. 3 of Zhigong Xincun Street, Xinghualing District, Taiyuan, Shanxi 030013, China

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Citation:
Zhang N, Ren Y, Wang Y, Zhao L, Wang B, Ma N, Gao Z, Cao B. LRG1 Suppresses Migration and Invasion of Esophageal Squamous Cell Carcinoma by Modulating Epithelial to Mesenchymal Transition. J Cancer 2020; 11(6):1486-1494. doi:10.7150/jca.36189. Available from https://www.jcancer.org/v11p1486.htm

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Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. The molecular pathogenesis underlying ESCC remains to be explored. Leucine-rich ɑ-2-glycoprotein 1 (LRG1) has been implicated in the pathogenesis of various cancer types, however its role in ESCC is unknown.

Materials and Methods: Data from the public database was analyzed to address the expression of LRG1 in ESCC. Gain-of-function studies were performed in select ESCC cell lines by over-expression or addition of recombinant LRG1, while loss-of-function studies achieved by small interfering RNA mediated knockdown. Wound healing and transwell assays were conducted to investigate ESCC cell migration and invasion upon manipulating LRG1 levels. Western blot and Immunofluorescence staining were used to examine the changes in epithelial to mesenchymal transition (EMT) and TGFβ signaling pathway.

Results: LRG1 mRNA levels were found to be significantly down-regulated in patients with ESCC as well as in several ESCC cell lines. Silencing of LRG1 promoted, while overexpression of LRG1 inhibited ESCC cell migration and invasion. In line with this, Silencing of LRG1 enhanced, while overexpression of LRG1 reduced TGFβ signaling and EMT of ESCC cells.

Conclusion/Significance: LRG1 suppresses ESCC cell migration and invasion via negative modulation of TGFβ signaling and EMT. Down-regulation of LRG1 in ESCC patients may favor tumor metastasis and disease progression.

Keywords: LRG1, Esophageal Squamous Cell Carcinoma, Migration, Invasion, Epithelial to Mesenchymal Transition, TGFβ signaling