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Updated: Jun 12, 2025
Combined Conditional Knockdown and Adapted Sphere Formation Assay to Study a Stemness-Associated Gene of Patient-derived Gastric Cancer Stem Cells
Published on: May 9, 2020
SCAMP1 silencing inhibits proliferation by attenuating multiple pro-survival signaling pathways in gastric cancer
Gang Ma1, Yang Yang2, Fenglin Cai1
1Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Tianjin Key Laboratory of Digestive Cancer, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, P. R. China.
Abstract:
Secretory carrier-associated membrane protein 1 (SCAMP1) is the most universally expressed member of the SCAMP family, and its ability to facilitate endocytosis was demonstrated approximately two decades ago. Nevertheless, its roles in cancer biology are largely unknown, although its expression is significantly increased in most cancer types. Herein, we examined the expression of SCAMP1 in gastric cancer (GC) tissues and found that it was aberrantly increased and positively correlated with tumor size and lymph node metastasis. More importantly, increased SCAMP1 expression was associated with poor prognosis in patients with GC. Functional experiments demonstrated that SCAMP1 knockdown markedly suppressed the proliferation of GC cells in vitro and in vivo. RNA sequencing assays demonstrated that SCAMP1 knockdown altered the expression profile of GC cells, and a significant portion of the altered genes were enriched in receptor tyrosine kinases and their related downstream signaling pathways. Immunoblotting confirmed that the Akt/MAPK/Stat signaling pathway was strongly attenuated in GC cells with SCAMP1 depletion. Taken together, these results demonstrated that SCAMP1 drives hyperproliferation in GC cells, thus suggesting that further investigation into the mechanisms and translational value of SCAMP1 in treating patients with GC is warranted.
Insights
Secretory carrier-associated membrane protein 1 (SCAMP1) drives gastric cancer (GC) cell hyperproliferation. SCAMP1 knockdown suppressed tumor growth and revealed its role in key signaling pathways, suggesting therapeutic potential.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- Secretory carrier-associated membrane protein 1 (SCAMP1) facilitates endocytosis but its role in cancer is largely unknown.
- SCAMP1 expression is elevated in most cancer types, including gastric cancer (GC).
Purpose of the Study:
- To investigate the expression and function of SCAMP1 in gastric cancer.
- To determine the prognostic significance of SCAMP1 in GC patients.
- To elucidate the molecular mechanisms underlying SCAMP1-driven GC progression.
Main Methods:
- Analysis of SCAMP1 expression in GC tissues.
- In vitro and in vivo functional assays following SCAMP1 knockdown.
- RNA sequencing to identify altered gene expression profiles.
- Western blotting to assess signaling pathway activation.
Main Results:
- SCAMP1 expression was significantly increased in GC tissues and correlated with tumor size and lymph node metastasis.
- Increased SCAMP1 expression was associated with poor prognosis in GC patients.
- SCAMP1 knockdown suppressed GC cell proliferation in vitro and in vivo.
- SCAMP1 depletion altered gene expression, particularly in receptor tyrosine kinase pathways, and attenuated the Akt/MAPK/Stat signaling pathway.
Conclusions:
- SCAMP1 drives hyperproliferation in gastric cancer cells.
- SCAMP1 represents a potential therapeutic target for gastric cancer.
- Further research into SCAMP1's mechanisms and translational value in GC is warranted.
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