2. Academic Validation
  3. Hedgehog/Gli2 signaling triggers cell proliferation and metastasis via EMT and wnt/β-catenin pathways in oral squamous cell carcinoma

Hedgehog/Gli2 signaling triggers cell proliferation and metastasis via EMT and wnt/β-catenin pathways in oral squamous cell carcinoma

  • Heliyon. 2024 Aug 17;10(16):e36516. doi: 10.1016/j.heliyon.2024.e36516.
Xiaotang Wang 1 2,  Xiaona Song 1 2,  Jiping Gao 1,  Guoqiang Xu 1 2,  Xiaoru Yan 1 2,  Junting Yang 1 2,  Yiyan Yang 1 2,  Guohua Song 1 2
Affiliations

Affiliations

  • 1 Laboratory Animal Center, Shanxi Medical University, Taiyuan, China.
  • 2 Department of Basic Medical Sciences, Shanxi Medical University, No 56, Xinjian South Rd, Taiyuan 030001, China.
PMID: 39253258 DOI: 10.1016/j.heliyon.2024.e36516
Abstract

Background: Oral squamous cell carcinoma (OSCC) is the most lethal oral malignant tumor, however, clinical outcomes remain unsatisfactory. The Hedgehog/Gli2 pathway plays a pivotal role in tumor progression, yet the regulatory mechanism governing its involvement in the malignant evolution process of OSCC remains elusive.

Methods: OSCC animal tissue samples were used to detect the activation of the Hedgehog/Gli2 pathway in OSCC. Based on the clinical information of oral Cancer patients in TCGA database, the role of this pathway in patients was analyzed, and the activation status of this pathway was verified in human OSCC cells. After activating or inhibiting the Hedgehog pathway, the effects of this pathway on the biological function of OSCC cells and its regulatory mechanism were examined. Interfering the expression of Gli2, a key transcription factor in this pathway, revealed the role of Hedgehog/Gli2 pathway in the malignant evolution of OSCC cells.

Results: The Hedgehog pathway exhibits abnormal activation in animal models of OSCC. Clinical data from TCGA demonstrate a significant enrichment of the Hedgehog pathway in patients with OSCC, and Gli2, a key downstream factor of this pathway, is closely associated with the occurrence and progression of OSCC. Cellular studies have revealed aberrant activation of this pathway in human OSCC cells, which exerts its function by modulating the activation of epithelial-mesenchymal transition (EMT) and Wnt/β-catenin pathways. Subsequent investigations further confirm the pivotal involvement of Gli2 in the Hedgehog pathway activation, underscoring its potential as a therapeutic target for inhibiting malignant proliferation and metastasis of OSCC cells through modulation of EMT and Wnt/β-catenin pathways.

Conclusion: The Hedgehog/Gli2 pathway induces EMT and activates Wnt/β-catenin pathway to trigger the malignant proliferation and metastasis of OSCC cells, and Gli2 plays a key role in this process, which suggests that targeting Gli2 may be a promising therapeutic strategy for inhibiting the proliferation and metastasis of OSCC.

Keywords

Cell metastasis; Cell proliferation; EMT; Hedgehog/Gli2 pathway; OSCC; Wnt/β-catenin.

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