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

Abstract

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.

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Acknowledgements

We thank Edanz Group (http://www.edanzediting.com/ac) for editing a draft of this manuscript.

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Correspondence to Mitsuro Kanda.

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All procedures performed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Nagoya University’s ethics committee approved this study (Approval number 2014-0043). All institutional and national guidelines for the care and use of laboratory animals were followed and were approved by Nagoya University Animal Research Committee (approval number 30143).

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Umeda, S., Kanda, M., Shimizu, D. et al. Lysosomal-associated membrane protein family member 5 promotes the metastatic potential of gastric cancer cells. Gastric Cancer 25, 558–572 (2022). https://doi.org/10.1007/s10120-022-01284-y

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  • DOI: https://doi.org/10.1007/s10120-022-01284-y

Keywords

  • LAMP5
  • Gastric cancer
  • Metastasis
  • Transcriptome