Inhibition of Sonic Hedgehog signaling pathway by GANT61 alleviates adenomyosis by suppressing epithelial-to-mesenchymal transition, cell migration and proliferation

Zaifan Lin, Lin Z, Yan S, Simiao Yan, Qingzhen Ran, Ran Q, Yang Q, Qianxin Yang, Lin H, Haixin Lin, Jingtong Sun, Sun J, Yi Chen, Chen Y, Zhong X, Xiuchi Zhong, Yingzhou Tian, Tian Y, Wanqun Chen, Chen W
Tissue & cell · 2026 · vol. 102 , pp. 103581 · doi:10.1016/j.tice.2026.103581 · PMID:42155541 · W7161399169
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⚙ AI-generated summary by claude@2026-06, 2026-06-06 ⓘ

GANT61 inhibited the Sonic Hedgehog signaling pathway to alleviate adenomyosis by suppressing epithelial-to-mesenchymal transition, cell migration, and proliferation.

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Abstract

Adenomyosis (ADM) is a benign condition associated with various gynecological disorders. However, effective treatment options are limited, highlighting the urgent need for novel therapeutic targets. This study identified abnormal activation of Hedgehog signaling pathway in tamoxifen-induced ADM mice. Inhibition of Hedgehog pathway by GANT61, a Glioma-associated oncogene 1/2 (Gli1/Gli2) inhibitor, significantly reduced the expression of Sonic Hedgehog signaling-related proteins. Ishikawa cells were treated with GANT61 to investigate the effect of Hedgehog signaling pathway inhibition on cell proliferation, migration, and invasion. The expression levels of related proteins were assessed by western blot. Cell phenotype experiments, including colony formation assay, 5-Ethynyl-2'-Deoxyuridine (EdU) assay, wound healing assay, and Transwell assay, were conducted. To validate the in vivo results, an adenomyosis mouse model was established and treated with GANT61. Western blot and immunohistochemistry were performed to measure the expression levels of key proteins. We demonstrated that Hedgehog signaling pathway specifically the Sonic Hedgehog signaling pathway (Shh) is abnormally active in adenomyosis and that GANT61 inhibited Shh signaling pathway, leading to a downregulation of Hedgehog pathway-related proteins and a reduction in cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) both in vivo and in vitro. These findings underscore the pivotal role of Shh signaling pathway in adenomyosis pathogenesis and demonstrate that its inhibition by GANT61 effectively mitigates disease-associated histopathological progression in a mouse model. This study uncovers a novel pathological mechanism and proposes a promising therapeutic strategy for adenomyosis.

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Condition tags

adenomyosis

MeSH descriptors

Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Cell Movement Cell Movement Cell Movement Cell Movement Cell Movement Cell Movement Cell Movement

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (27)

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