SEC22B inhibition attenuates colorectal cancer aggressiveness and autophagic flux under unfavorable environment

Jang Hyun Choi, So Yeon Park, Won Jae Lee, Choong Jae Lee, Jee Heun Kim, Tae Young Jang, So El Jeon, Youngsoo Jun, Jeong Seok Nam

Research output: Contribution to journalArticlepeer-review

Abstract

Autophagy has bidirectional functions in cancer by facilitating cell survival and death in a context-dependent manner. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are a large family of proteins essential for numerous biological processes, including autophagy; nevertheless, their potential function in cancer malignancy remains unclear. Here, we explored the gene expression patterns of SNAREs in tissues of patients with colorectal cancer (CRC) and discovered that SEC22B expression, a vesicle SNARE, was higher in tumor tissues than in normal tissues, with a more significant increase in metastatic tissues. Interestingly, SEC22B knockdown dramatically decreased CRC cell survival and growth, especially under stressful conditions, such as hypoxia and serum starvation, and decreased the number of stress-induced autophagic vacuoles. Moreover, SEC22B knockdown successfully attenuated liver metastasis in a CRC cell xenograft mouse model, with histological signs of decreased autophagic flux and proliferation within cancer cells. Together, this study posits that SEC22B plays a crucial role in enhancing the aggressiveness of CRC cells, suggesting that SEC22B might be an attractive therapeutic target for CRC.

Original languageEnglish
Pages (from-to)10-18
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume665
DOIs
StatePublished - 12 Jul 2023

Bibliographical note

Publisher Copyright:
© 2023

Keywords

  • Autophagy
  • Colorectal cancer
  • Hypoxia
  • Metastatic colonization
  • SEC22B
  • Starvation

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