Research Article: STC1 promotes colorectal cancer invasion and migration by regulating M2 macrophage polarization via TGF-?1/Smad signaling pathway
Abstract:
Colorectal cancer (CRC) mortality is largely attributable to invasion, migration, and an immunosuppressive tumor microenvironment. We examined the clinical relevance and mechanistic function of stanniocalcin-1 (STC1) in CRC, with emphasis on macrophage polarization.
STC1 expression patterns, prognostic value, and associated pathways were analyzed in TCGA and GEO CRC datasets, followed by KEGG enrichment. STC1 was silenced in HCT116 and SW620 cells using siRNA. Wound-healing and Transwell migration/invasion assays, immunofluorescence, qRT-PCR, ELISA and Western blotting were performed to evaluate metastatic phenotypes, epithelial–mesenchymal transition (EMT), and TGF-?1/Smad signaling. Correlations between STC1 and immune infiltration were assessed in TCGA. Conditioned-medium and co-culture experiments, together with flow cytometry analysis of M2-associated surface markers were used to determine the impact of STC1 on macrophage polarization and the reciprocal effects of polarized macrophages on CRC cell behavior.
STC1 was significantly upregulated in CRC, and high STC1 expression was associated with worse overall and disease-free survival. STC1 knockdown markedly reduced CRC cell migration and invasion and attenuated EMT, as evidenced by increased E-cadherin and decreased N-cadherin/vimentin. Bioinformatic and experimental analyses indicated that STC1 promotes CRC progression via activation of the TGF-?1/Smad pathway. STC1 levels correlated positively with macrophage infiltration in CRC tissues. In vitro , STC1 promoted M2 macrophage polarization, while M2 macrophages enhanced EMT and metastatic traits of CRC cells, supporting a pro-tumor positive-feedback loop.
STC1 facilitates CRC invasion and migration by activating TGF-?1/Smad signaling and driving M2 macrophage polarization, suggesting its utility as a prognostic biomarker and therapeutic target.
Introduction:
Malignancies represent a major and growing global health burden. Colorectal cancer (CRC) ranks among the most frequently diagnosed cancers worldwide and remains a leading cause of cancer-related death ( 1 ). Despite improvements in multimodal therapies, including neoadjuvant chemotherapy, the overall 5-year survival rate for CRC has not increased substantially ( 2 ). Therefore, uncovering key molecular factors and immune-related mechanisms that drive CRC is essential for developing more effective targeted…
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