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Background  Adenocarcinoma of the esophagogastric junction (AEG) refers to cancer that crosses the line of the gastroesophageal junction and includes distal esophageal cancer and proximal gastric cancer. It is characterized by early metastasis and a poor prognosis and has few treatment options. Here, we report a novel potential therapeutic target, hematological and neurological expressed 1‐like ( HN1L ), in AEG.    Methods  A total of 38 patients who underwent surgical resection of AEG at the Department of Thoracic Surgery of Shandong Provincial Hospital from September 2018 to June 2019 were enrolled into the study. We detected the expression of HN1L in AEG and adjacent nontumor tissues by IHC staining. The clinicopathological characteristics of  HN1L  were statistically analyzed. Then, the expression of  HN1L  in different cell lines was detected by RT‐q PCR. Finally, AGS and HGC‐27 cell lines were performed to inhibit  HN1L  by sh RNA  in order to explore its role in the development of AEG.    Results  Immunohistochemical staining showed that the expression of HN1L in cancer tissues was higher than that in nontumor tissue ( p  < 0.001). High expression of HN1L was significantly correlated with TNM stage ( p  = 0.013) and lymph node metastasis ( p  = 0.03). The expression of  HN1L  was upregulated in tumor cell lines compared with normal cell line. Additionally, Cell function studies demonstrated that lentivirus‐mediated sh RNA  silencing of  HN1L  expression could effectively reduce the proliferation, invasion, and metastasis of tumor cell lines and promote their apoptosis ( p  < 0.05).    Conclusions   HN1L  expression might contribute to the invasion and metastasis of AEG and is a promising therapeutic target.

HN1L promotes invasion and metastasis of the esophagogastric junction adenocarcinoma