[SCAMP2-EGR1 axis induces apoptosis and suppresses growth of colorectal cancer cells].

Objective: To investigate the molecular mechanisms by which secretory carrier membrane protein 2 (SCAMP2) contributes to colorectal cancer cell proliferation via regulating early growth response factor 1 (EGR1). Methods: Ten pairs of pathologically confirmed colorectal cancer tissues and adjacent non-tumor tissues were collected at the Affiliated Hospital of Qingdao University between January 2022 and March 2023. The expression of SCAMP2 was examined using Western blot and immunohistochemistry. SW480 and HT29 cell lines were transfected with small interfering RNA (siRNA), short hairpin RNA (shRNA) and SCAMP2/EGR1 overexpression plasmids to establish cell models with SCAMP2 or EGR1 overexpression and knockdown. Cell counting kit-8 (CCK8) assay, flow cytometry and nude mouse subcutaneous tumorigenesis assay were performed to evaluate the effects of SCAMP2 expression on the proliferation and apoptosis of colorectal cancer cells. Transcriptome sequencing was performed to identify early growth response factor 1 (EGR1) as the downstream regulatory factor of SCAMP2. Rescue experiments were used to confirm the interaction between SCAMP2 and EGR. Results: Western blot demonstrated that the expression level of SCAMP2 in 7 pairs of colorectal cancer tissues was lower than that in adjacent normal intestinal tissues. Immunohistochemistry revealed that SCAMP2 showed strongly positive staining (3+) in normal intestinal epithelium, but negative/weakly positive staining (1+) in colorectal cancer. Consistently, EGR1 exhibited strongly positive immunoreactivity (3+) in normal intestinal epithelium, but negative/weak positive staining (1+) in colorectal cancer. In vitro cellular experiments confirmed that overexpression of SCAMP2 or EGR1 significantly suppressed the proliferation of colorectal cancer cells (all P<0.05). Furthermore, the nude mouse xenograft tumor model showed that SCAMP2 overexpression remarkably inhibited tumor growth in vivo (P<0.05). Transcriptome sequencing showed that the mRNA expression level of EGR1 was significantly up-regulated in SCAMP2-overexpressing colorectal cancer cells (P<0.05). Rescue experiments illustrated that knockdown of EGR1 partially reversed the inhibitory effects on cell proliferation and pro-apoptotic effects induced by SCAMP2 overexpression. Conversely, overexpression of EGR1 partially abrogated the enhanced proliferation and reduced apoptosis triggered by SCAMP2 knockdown. Conclusions: SCAMP2 expression is downregulated in colorectal cancer. Low SCAMP2 expression may impair EGR1 signaling, thereby suppressing apoptosis and promoting colorectal cancer cell proliferation. The SCAMP2/EGR1 signaling axis plays a crucial role in colorectal cancer progression.