Lysosomal-associated membrane protein family member 5 promotes the metastatic potential of gastric cancer cells

• Published in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2022-05, Vol.25 (3), p.558-572
• Main Authors: Umeda, Shinichi, Kanda, Mitsuro, Shimizu, Dai, Nakamura, Shunsuke, Sawaki, Koichi, Inokawa, Yoshikuni, Hattori, Norifumi, Hayashi, Masamichi, Tanaka, Chie, Nakayama, Goro, Kodera, Yasuhiro
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Apoptosis; Autophagy; Cancer Research; Cell cycle; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Drug development; Family; Gastric cancer; Gastroenterology; Gene Expression Regulation, Neoplastic; Genes; Humans; Liver; Liver Neoplasms - secondary; Lysosomal Membrane Proteins - genetics; Lysosomal Membrane Proteins - metabolism; Medicine; Medicine & Public Health; Membrane proteins; Metastases; Metastasis; Molecular modelling; Oncology; Original Article; Peritoneum; Prognosis; Proteomes; Stomach Neoplasms - pathology; Surgical Oncology; Transcriptomes; Tumors; Xenografts
• ISSN: 1436-3291; 1436-3305
• DOI: 10.1007/s10120-022-01284-y

Background Metastatic gastric cancer (GC) has a poor prognosis, and elucidating the molecular mechanisms involved in metastasis may lead to the development of novel therapeutic modalities. Methods Transcriptome analysis of surgically resected metastatic tissue from GC patients and noncancerous tissue was performed to identify novel metastasis-related genes. Analyses of in vitro cell function, apoptosis, the cell cycle and cancer stemness were performed using GC cell lines with a stable knockout of a candidate gene. In vivo percutaneous, peritoneal dissemination and liver metastasis xenograft models were also generated. PCR array and proteome analyses were performed. Expression of the candidate gene was analyzed in GC tissues from 300 patients. Results Lysosomal Associated Membrane Protein Family Member 5 ( LAMP5 ) was upregulated in the metastatic tissues. LAMP5 knockout significantly suppressed proliferation, invasion, and migration of GC cells and increased apoptosis, cell cycle arrest and cancer stemness. LAMP5 knockout virtually suppressed tumor growth in in vivo percutaneous, peritoneal dissemination and liver metastasis models. EMT- and autophagy-related genes were associated with LAMP5 . High LAMP5 mRNA levels were significantly associated with a worse prognosis. Conclusion LAMP5 plays a vital role in metastasis formation and may be a promising novel target of drug development for metastatic GC in the future.