| First Author | Guo P | Year | 2022 |
| Journal | Oncogene | Volume | 41 |
| Issue | 20 | Pages | 2846-2859 |
| PubMed ID | 35418691 | Mgi Jnum | J:324775 |
| Mgi Id | MGI:7281666 | Doi | 10.1038/s41388-022-02308-8 |
| Citation | Guo P, et al. (2022) Nuclear receptor coactivator SRC-1 promotes colorectal cancer progression through enhancing GLI2-mediated Hedgehog signaling. Oncogene 41(20):2846-2859 |
| abstractText | Overexpression of nuclear coactivator steroid receptor coactivator 1 (SRC-1) and aberrant activation of the Hedgehog (Hh) signaling pathway are associated with various tumorigenesis; however, the significance of SRC-1 in colorectal cancer (CRC) and its contribution to the activation of Hh signaling are unclear. Here, we identified a conserved Hh signaling signature positively correlated with SRC-1 expression in CRC based on TCGA database; SRC-1 deficiency significantly inhibited the proliferation, survival, migration, invasion, and tumorigenesis of both human and mouse CRC cells, and SRC-1 knockout significantly suppressed azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CRC in mice. Mechanistically, SRC-1 promoted the expression of GLI family zinc finger 2 (GLI2), a major downstream transcription factor of Hh pathway, and cooperated with GLI2 to enhance multiple Hh-regulated oncogene expression, including Cyclin D1, Bcl-2, and Slug. Pharmacological blockages of SRC-1 and Hh signaling retarded CRC progression in human CRC cell xenograft mouse model. Together, our studies uncover an SRC-1/GLI2-regulated Hh signaling looping axis that promotes CRC tumorigenesis, offering an attractive strategy for CRC treatment. |
