G-protein subunit gamma-4 expression has potential for detection, prediction and therapeutic targeting in liver metastasis of gastric cancer
| Autor: | Daisuke Kobayashi, Haruyoshi Tanaka, Chie Tanaka, Suguru Yamada, Yasuhiro Kodera, Goro Nakayama, Masamichi Hayashi, Masahiko Koike, Shinichi Umeda, Koichi Sawaki, Takashi Miwa, Mitsuro Kanda |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Cancer Research medicine.disease_cause Article Metastasis Transcriptome Gene Knockout Techniques Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Movement Stomach Neoplasms Cell Line Tumor GTP-Binding Protein gamma Subunits Animals Humans Medicine Cell Proliferation Neoplasm Staging Gene knockdown business.industry Gene Expression Profiling Liver Neoplasms Cancer Cell cycle Prognosis medicine.disease Survival Analysis Xenograft Model Antitumor Assays Phenotype Up-Regulation Gene Expression Regulation Neoplastic Oncology Gene Knockdown Techniques 030220 oncology & carcinogenesis Cancer research Female business Carcinogenesis Neoplasm Transplantation |
| Zdroj: | Br J Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/s41416-021-01366-1 |
| Popis: | Background The liver is the most common site for haematogenous metastasis of gastric cancer, and liver metastasis is fatal. Methods We conducted a transcriptomic analysis between metastatic foci in the liver, primary tumour and adjacent tissues from gastric cancer patients with metastasis limited to the liver. We determined mRNA expression levels in tumour tissues of 300 patients with gastric cancer via quantitative RT-PCR. The oncogenic phenotypes of GNG4 were determined with knockdown, knockout and forced expression experiments. We established and compared subcutaneous and liver metastatic mouse xenograft models of gastric cancer to reveal the roles of GNG4 in tumorigenesis in the liver. Results GNG4 was upregulated substantially in primary gastric cancer tissues as well as liver metastatic lesions. High levels of GNG4 in primary cancer tissues were associated with short overall survival and the likelihood of liver recurrence. Functional assays revealed that GNG4 promoted cancer cell proliferation, the cell cycle and adhesiveness. Tumour formation by GNG4-knockout cells was moderately reduced in the subcutaneous mouse model and strikingly attenuated in the liver metastasis mouse model. Conclusions GNG4 expression may provide better disease monitoring for liver metastasis, and GNG4 may be a novel candidate therapeutic target for liver metastasis. |
| Databáze: | OpenAIRE |
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