Oncogene OSTM1 Promotes Gastric-Cancer Metastasis by Modulating the Metastatic Microenvironment Through Altered Tumor-Cell Autocrine Signaling
Gastric cancer remains a malignancy with high incidence, mortality rates, and poor prognosis globally. Osteoclastogenesis-associated transmembrane protein 1 (OSTM1), a transmembrane protein overexpressed in various tumors, has unclear functions in gastric-cancer progression. This study explores OSTM...
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2025-01-01
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| author | Yucheng Tang Yi Guo Jiangyi Feng Ziwei Wang |
| author_facet | Yucheng Tang Yi Guo Jiangyi Feng Ziwei Wang |
| author_sort | Yucheng Tang |
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| description | Gastric cancer remains a malignancy with high incidence, mortality rates, and poor prognosis globally. Osteoclastogenesis-associated transmembrane protein 1 (OSTM1), a transmembrane protein overexpressed in various tumors, has unclear functions in gastric-cancer progression. This study explores OSTM1’s role in gastric-cancer proliferation and metastasis. OSTM1 expression was analyzed in gastric-cancer and adjacent tissues using immunohistochemistry and RT-qPCR. OSTM1 overexpression and knockdown cell lines were established to assess its effects on cancer-cell behavior through in vitro and in vivo experiments. Western blot and RT-qPCR were used to examine OSTM1’s regulation of S100A4 expression. OSTM1 was significantly overexpressed in gastric-cancer tissues, negatively correlating with TNM staging and overall survival. OSTM1 overexpression enhanced cancer-cell proliferation, colony formation, migration, and invasion, while its knockdown showed opposite effects. In vivo studies confirmed increased lung metastatic capability in high OSTM1-expressing cells. Mechanistically, OSTM1 positively regulated S100A4 expression, with S100A4 knockdown reducing OSTM1-enhanced metastasis. Gastric-cancer lung metastases showed higher microvascular density and α-SMA-positive fibroblast infiltration in the OSTM1 high-expression group. OSTM1 promotes gastric-cancer progression by upregulating S100A4 and modifying the tumor microenvironment through enhanced angiogenesis and fibroblast activation. OSTM1 represents a potential diagnostic and prognostic biomarker, with the OSTM1–S100A4 axis offering new therapeutic possibilities for gastric-cancer treatment. |
| format | Article |
| id | doaj-art-d07fd3f043af4a8b878d2b89669909a2 |
| institution | Kabale University |
| issn | 1467-3037 1467-3045 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-d07fd3f043af4a8b878d2b89669909a22025-01-24T13:27:35ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-01-014715510.3390/cimb47010055Oncogene OSTM1 Promotes Gastric-Cancer Metastasis by Modulating the Metastatic Microenvironment Through Altered Tumor-Cell Autocrine SignalingYucheng Tang0Yi Guo1Jiangyi Feng2Ziwei Wang3Department of General Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaChongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing 400014, ChinaChongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing 400014, ChinaDepartment of General Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaGastric cancer remains a malignancy with high incidence, mortality rates, and poor prognosis globally. Osteoclastogenesis-associated transmembrane protein 1 (OSTM1), a transmembrane protein overexpressed in various tumors, has unclear functions in gastric-cancer progression. This study explores OSTM1’s role in gastric-cancer proliferation and metastasis. OSTM1 expression was analyzed in gastric-cancer and adjacent tissues using immunohistochemistry and RT-qPCR. OSTM1 overexpression and knockdown cell lines were established to assess its effects on cancer-cell behavior through in vitro and in vivo experiments. Western blot and RT-qPCR were used to examine OSTM1’s regulation of S100A4 expression. OSTM1 was significantly overexpressed in gastric-cancer tissues, negatively correlating with TNM staging and overall survival. OSTM1 overexpression enhanced cancer-cell proliferation, colony formation, migration, and invasion, while its knockdown showed opposite effects. In vivo studies confirmed increased lung metastatic capability in high OSTM1-expressing cells. Mechanistically, OSTM1 positively regulated S100A4 expression, with S100A4 knockdown reducing OSTM1-enhanced metastasis. Gastric-cancer lung metastases showed higher microvascular density and α-SMA-positive fibroblast infiltration in the OSTM1 high-expression group. OSTM1 promotes gastric-cancer progression by upregulating S100A4 and modifying the tumor microenvironment through enhanced angiogenesis and fibroblast activation. OSTM1 represents a potential diagnostic and prognostic biomarker, with the OSTM1–S100A4 axis offering new therapeutic possibilities for gastric-cancer treatment.https://www.mdpi.com/1467-3045/47/1/55gastric cancerOSTM1S100A4proliferation and metastasistumor microenvironment |
| spellingShingle | Yucheng Tang Yi Guo Jiangyi Feng Ziwei Wang Oncogene OSTM1 Promotes Gastric-Cancer Metastasis by Modulating the Metastatic Microenvironment Through Altered Tumor-Cell Autocrine Signaling Current Issues in Molecular Biology gastric cancer OSTM1 S100A4 proliferation and metastasis tumor microenvironment |
| title | Oncogene OSTM1 Promotes Gastric-Cancer Metastasis by Modulating the Metastatic Microenvironment Through Altered Tumor-Cell Autocrine Signaling |
| title_full | Oncogene OSTM1 Promotes Gastric-Cancer Metastasis by Modulating the Metastatic Microenvironment Through Altered Tumor-Cell Autocrine Signaling |
| title_fullStr | Oncogene OSTM1 Promotes Gastric-Cancer Metastasis by Modulating the Metastatic Microenvironment Through Altered Tumor-Cell Autocrine Signaling |
| title_full_unstemmed | Oncogene OSTM1 Promotes Gastric-Cancer Metastasis by Modulating the Metastatic Microenvironment Through Altered Tumor-Cell Autocrine Signaling |
| title_short | Oncogene OSTM1 Promotes Gastric-Cancer Metastasis by Modulating the Metastatic Microenvironment Through Altered Tumor-Cell Autocrine Signaling |
| title_sort | oncogene ostm1 promotes gastric cancer metastasis by modulating the metastatic microenvironment through altered tumor cell autocrine signaling |
| topic | gastric cancer OSTM1 S100A4 proliferation and metastasis tumor microenvironment |
| url | https://www.mdpi.com/1467-3045/47/1/55 |
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