SEC31A promotes gastric cancer progression by inducing the PI3K/AKT/mTOR pathway and enhancing the CCL5-mediated M2 polarization and recruitment of tumor-associated macrophages
- 1Department of Gastroenterology, Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China
Abstract
SEC31 homolog A (SEC31A) is associated with a variety of cancers. This study elucidated the role of SEC31A in gastric cancer (GC). The expression of SEC31A in GC was analyzed using western blotting and immunohistochemistry. Functional experiments were performed to detect the impact of SEC31A on GC proliferation, migration and invasion. The PI3K inhibitor LY294002 was used to explore the regulation of the biological functions by SEC31A through the PI3K/AKT/mTOR pathway in GC cells. Co-culture of THP-1 (human leukemia cell line of monocytic origin) and GC cells was conducted to investigate the impact of SEC31A on the M2 macrophage polarization in tumor immune microenvironment. Our investigation observed elevated expression of SEC31A in both GC tissue and cell lines. Through functional studies, suppression of SEC31A was found to decrease epithelial-mesenchymal transition (EMT), proliferation, migration and invasion in GC cells. Overexpression of SEC31A led to activation of the PI3K/AKT/mTOR signaling cascade. The PI3K inhibitor LY294002 counteracted the increases in proliferation, migration, invasion and EMT triggered by SEC31A. Co-culture experiments involving THP-1 and GC cells indicated that SEC31A enhanced the recruitment and M2 polarization of macrophages via CCL5 within the GC tumor microenvironment (ME). To assess the influence of M2 macrophages on malignant behavior of GC cells, M2 macrophage-conditioned medium (M2-CM) was applied. M2-CM mitigated the inhibitory effects on malignant phenotypes in GC cells following SEC31A knockdown. Moreover, diminished SEC31A expression enhanced the efficacy of anti-PD-1 therapy in GC models. Collectively, SEC31A promoted GC progression via activating the PI3K/AKT/mTOR pathway and facilitating CCL5-mediated M2 polarization and recruitment of tumor-associated macrophages. SEC31A knockdown may augment the anti-tumor response to anti-PD-1 treatment in GC. These findings highlight SEC31A as a valuable prognostic indicator and potential target for immunotherapy in GC, offering novel strategies to enhance the effectiveness of anti-PD-1 therapy.
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BibTeX
@article{zhao2026sec31a,
title = {{SEC31A promotes gastric cancer progression by inducing the PI3K/AKT/mTOR pathway and enhancing the CCL5-mediated M2 polarization and recruitment of tumor-associated macrophages}},
author = {Xixian Zhao and Liuye Huang},
journal = {Oncology Reports},
year = {2026},
month = oct,
doi = {10.3892/or.2026.9211},
url = {https://doi.org/10.3892/or.2026.9211},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - SEC31A promotes gastric cancer progression by inducing the PI3K/AKT/mTOR pathway and enhancing the CCL5-mediated M2 polarization and recruitment of tumor-associated macrophages
AU - Xixian Zhao
AU - Liuye Huang
PY - 2026
DA - 2026/10/14
JO - Oncology Reports
DO - 10.3892/or.2026.9211
UR - https://doi.org/10.3892/or.2026.9211
AB - SEC31 homolog A (SEC31A) is associated with a variety of cancers. This study elucidated the role of SEC31A in gastric cancer (GC). The expression of SEC31A in GC was analyzed using western blotting and immunohistochemistry. Functional experiments were performed to detect the impact of SEC31A on GC proliferation, migration and invasion. The PI3K inhibitor LY294002 was used to explore the regulation of the biological functions by SEC31A through the PI3K/AKT/mTOR pathway in GC cells. Co-culture of THP-1 (human leukemia cell line of monocytic origin) and GC cells was conducted to investigate the impact of SEC31A on the M2 macrophage polarization in tumor immune microenvironment. Our investigation observed elevated expression of SEC31A in both GC tissue and cell lines. Through functional studies, suppression of SEC31A was found to decrease epithelial-mesenchymal transition (EMT), proliferation, migration and invasion in GC cells. Overexpression of SEC31A led to activation of the PI3K/AKT/mTOR signaling cascade. The PI3K inhibitor LY294002 counteracted the increases in proliferation, migration, invasion and EMT triggered by SEC31A. Co-culture experiments involving THP-1 and GC cells indicated that SEC31A enhanced the recruitment and M2 polarization of macrophages via CCL5 within the GC tumor microenvironment (ME). To assess the influence of M2 macrophages on malignant behavior of GC cells, M2 macrophage-conditioned medium (M2-CM) was applied. M2-CM mitigated the inhibitory effects on malignant phenotypes in GC cells following SEC31A knockdown. Moreover, diminished SEC31A expression enhanced the efficacy of anti-PD-1 therapy in GC models. Collectively, SEC31A promoted GC progression via activating the PI3K/AKT/mTOR pathway and facilitating CCL5-mediated M2 polarization and recruitment of tumor-associated macrophages. SEC31A knockdown may augment the anti-tumor response to anti-PD-1 treatment in GC. These findings highlight SEC31A as a valuable prognostic indicator and potential target for immunotherapy in GC, offering novel strategies to enhance the effectiveness of anti-PD-1 therapy.
SN - 1021-335X
SN - 1791-2431
ER -