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ELTD1 通过调节 CSK 通过 MAPK/ERK 信号传导促进胃癌细胞增殖、侵袭和上皮-间质转化
Authors Sun B, Zhong FJ
Received 24 June 2021
Accepted for publication 5 August 2021
Published 27 August 2021 Volume 2021:14 Pages 4897—4911
DOI https://doi.org/10.2147/IJGM.S325495
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Scott Fraser
Purpose: Patients with gastric cancer (GC) often die from metastasis. However, the exact molecular mechanism underlying GC metastasis is complicated and still remains elusive. Epidermal growth factor, latrophilin and seven-transmembrane domain-containing 1 (ELTD1), has been reported to be involved in cancer metastasis, but its role in GC is still missing.
Patients and Methods: We first analyzed the expression of ELTD1 in GC using public databases (TCGA, Oncomine, and GEO) and our clinical samples. The functions of ELTD1 in GC proliferation, invasion and metastasis were determined by in vitro and in vivo experiments. The functional mechanism of ETLD1 in GC was also investigated. Finally, the association between ELTD1 expression and the overall survival of GC patients was analyzed using public databases.
Results: ELTD1 is significantly upregulated in GC tissues. Knockdown of ELTD1 inhibits GC cell proliferation, migration and invasion in vitro as well as tumor growth and metastasis in vivo, while ELTD1 overexpression obtains opposite results. Moreover, ELTD1 could promote epithelial to mesenchymal transition (EMT) in GC. Mechanistically, ELTD1 exerts its tumor-promoting effect by activating MAPK/ERK signaling. Subsequent studies demonstrated that ELTD1 could interact with C-terminal Src kinase (CSK) and inhibit its expression, which finally lead to MAPK/ERK activation. Data from TGCA and GEO both revealed that GC patients with high ELTD1 expression had poorer prognosis and the combination of ELTD1 with CSK showed better predictive performance.
Conclusion: ELTD1 plays an oncogene role in GC through MAPK/ERK signaling via inhibiting CSK, which may be a useful prognostic predictor and potential therapeutic target for GC.
Keywords: epidermal growth factor, latrophilin and seven-transmembrane domain-containing 1, EMT, C-terminal Src kinase, prognosis