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<p>Gastric cancer (GC) is a neoplasia with an increase in incidence and mortality over the next years. Currently, the treatment of this malignancy consists of surgery in association with the administration of platinum compounds or 5-FU capecitabine. The identification of novel biomarkers related to the GC progression is a key point in re-modulating the pharmacological treatment to get a more efficient patient response. In this study, we reported that Hormonally Upregulated Neu tumor-associated Kinase (HUNK) promotes gastric cancer progression by regulating cell homeostasis. Particularly, we demonstrated that HUNK is responsible for the increase in gastric cancer cell proliferation through the binding and phosphorylation of p38 MAP kinase and that its depletion is associated with a reduction of survival both in gastric cancer cells and patient-derived organoids. Further, we reported that HUNK regulates positively the expression of MUC16/CA-125, a well-known cancer prognostic marker. Our findings shed light, for the first time, on the molecular mechanisms regulated by HUNK in gastric cancer cells making this kinase a promising candidate for novel targeted therapeutic strategies.</p>

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Hormonally upregulated neu tumor-associated kinase (HUNK) modulates gastric cancer progression through the regulation of cell homeostasis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • Giuseppina di Paola,
  • Francesco Albano,
  • Pietro Zoppoli,
  • Daniele Bravoco,
  • Teresa D’Amore,
  • Elena Amendola,
  • Valeria Lucci,
  • Luca Roberto,
  • Mariarita Brancaccio,
  • Paolo Salerno,
  • Giovanni Calice,
  • Simona Laurino,
  • Sabino Russi,
  • Cristofaro De Stefano,
  • Monica Maiello,
  • Giuseppe Merla,
  • Geppino Falco,
  • Pellegrino Mazzone

摘要

Gastric cancer (GC) is a neoplasia with an increase in incidence and mortality over the next years. Currently, the treatment of this malignancy consists of surgery in association with the administration of platinum compounds or 5-FU capecitabine. The identification of novel biomarkers related to the GC progression is a key point in re-modulating the pharmacological treatment to get a more efficient patient response. In this study, we reported that Hormonally Upregulated Neu tumor-associated Kinase (HUNK) promotes gastric cancer progression by regulating cell homeostasis. Particularly, we demonstrated that HUNK is responsible for the increase in gastric cancer cell proliferation through the binding and phosphorylation of p38 MAP kinase and that its depletion is associated with a reduction of survival both in gastric cancer cells and patient-derived organoids. Further, we reported that HUNK regulates positively the expression of MUC16/CA-125, a well-known cancer prognostic marker. Our findings shed light, for the first time, on the molecular mechanisms regulated by HUNK in gastric cancer cells making this kinase a promising candidate for novel targeted therapeutic strategies.