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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41388-022-02308-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
D1 Receptor Functional Asymmetry at Striatonigral Neurons: A Neurochemical and Behavioral Study in Male Wistar Rats.
J Neurosci Res
January 2025
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de Mexico, Mexico.
Lateralization of motor behavior, a common phenomenon in humans and several species, is modulated by the basal ganglia, a site pointed out for the interhemispheric differences related to lateralization. Our study aims to shed light on the potential role of the striatonigral D1 receptor in functional asymmetry in normal conditions through neurochemical and behavioral means. We found that D1 receptor activation and D1/D3 receptor coactivation in striatonigral neurons leads to more cAMP production by adenylyl cyclase in the striatum and GABA release in their terminals in the right hemisphere compared to the left.
View Article and Find Full Text PDFMicroRNA-668 alleviates renal fibrosis through PPARα/PGC-1α pathway.
Eur J Med Res
December 2024
Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China.
Background: The involvement of microRNA-668 (miR-668) in the onset and progression of renal fibrosis remains unclear. To this end, we aimed to explore the relevant mechanism of miR-668 in renal fibrosis.
Methods: C57BL/6 J male mice were randomly divided into sham-operated, unilateral ureteral obstruction (UUO), and UUO-fenofibrate groups.
Ferritinophagy promotes microglia ferroptosis to aggravate neuroinflammation induced by cerebral ischemia-reperfusion injury via activation of the cGAS-STING signaling pathway.
Neurochem Int
December 2024
Department of Anesthesiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; Heilongjiang Province Key Laboratory of Research on Anesthesiology and Critical Care Medicine, Harbin, 150001, China. Electronic address:
Cerebral ischemia-reperfusion injury (CIRI) is a common and serious complication of reperfusion therapy in patients with ischemic stroke (IS). The regulation of microglia-mediated neuroinflammation to control CIRI has garnered considerable attention. The balance of iron metabolism is key to maintaining the physiological functions of microglia.
View Article and Find Full Text PDFAdipocyte-derived ferroptotic signaling mitigates obesity.
Cell Metab
December 2024
The Second Affiliated Hospital, School of Public Health, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou 310058, China; School of Public Health, Basic Medical Sciences, School of Pharmacology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China; School of Public Health, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China. Electronic address:
Ferroptosis is characterized as an iron-dependent and lipophilic form of cell death. However, it remains unclear what role ferroptosis has in adipose tissue function and activity. Here, we find a lower ferroptotic signature in the adipose tissue of individuals and mice with obesity.
View Article and Find Full Text PDFTherapeutic potential of 5-aminolevulinic acid in metabolic disorders: Current insights and future directions.
iScience
December 2024
Poltava State Medical University, Department of Pathophysiology, Poltava, Ukraine.
5-Aminolevulinic acid (5-ALA) is an essential compound in the biosynthesis of heme, playing a critical role in various physiological processes within the human body. This review provides the thorough analysis of the latest research on the molecular mechanisms and potential therapeutic benefits of 5-ALA in managing metabolic disorders. The ability of 5-ALA to influence immune response and inflammation, oxidative/nitrosative stress, antioxidant system, mitochondrial functions, as well as carbohydrate and lipid metabolism, is mediated by molecular mechanisms associated with the suppression of the transcription factor NF-κB signaling pathway, activation of the transcription factor Nrf2/heme oxygenase-1 (HO-1) system leading to the formation of heme-derived reaction products (carbon monoxide, ferrous iron, biliverdin, and bilirubin), which may contribute to HO-1-dependent cytoprotection through antioxidant and immunomodulatory effects.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!