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<p>Liver cancer is one of the most prevalent types of cancer worldwide with less than 20% of patients surviving in the past half a decade. Several molecular pathways have been uncovered that may lead to the development of liver cancer but more recently the Hedgehog pathway (HH) and its interactions with the gut microbiota has emerged as an underlying cause of the development of liver cancer. Gut-liver axis is vital to maintaining homeostasis. The HH pathway controls cellular differentiation, proliferation, and apoptosis evasions, its abnormal activation can lead to uncontrolled proliferation of liver cancer stem cells. Additionally, the intricate interplay between HH signaling and the gut microbiota introduces a novel dimension. Recent investigations suggest that potential modulation of HH activity by gut microbiota influence HCC progression. This review explores a crosstalk between HH signaling and the gut microbiota, uncovering intricate mechanisms by which it fuels liver cancer development. This interplay provides insights into gut dysbiosis, HCC etiology and potential therapeutic avenues, highlighting the cooperative role of HH signaling and gut microbiota in shaping the overall HCC landscape.</p>

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Understanding the role of Hedgehog signaling pathway and gut dysbiosis in fueling liver cancer

  • 期刊论文

  • 发表日期：

    2025年4月22日

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  • Naz Fatima,
  • Hooriya Fatima,
  • Sadia Ahmad,
  • Muhammad Abu Talha Safdar Hashmi,
  • Nadeem Sheikh

摘要

Liver cancer is one of the most prevalent types of cancer worldwide with less than 20% of patients surviving in the past half a decade. Several molecular pathways have been uncovered that may lead to the development of liver cancer but more recently the Hedgehog pathway (HH) and its interactions with the gut microbiota has emerged as an underlying cause of the development of liver cancer. Gut-liver axis is vital to maintaining homeostasis. The HH pathway controls cellular differentiation, proliferation, and apoptosis evasions, its abnormal activation can lead to uncontrolled proliferation of liver cancer stem cells. Additionally, the intricate interplay between HH signaling and the gut microbiota introduces a novel dimension. Recent investigations suggest that potential modulation of HH activity by gut microbiota influence HCC progression. This review explores a crosstalk between HH signaling and the gut microbiota, uncovering intricate mechanisms by which it fuels liver cancer development. This interplay provides insights into gut dysbiosis, HCC etiology and potential therapeutic avenues, highlighting the cooperative role of HH signaling and gut microbiota in shaping the overall HCC landscape.