di Paola Giuseppina, Albano Francesco, Zoppoli Pietro, Bravoco Daniele, D'Amore Teresa, Amendola Elena, Lucci Valeria, Roberto Luca, Brancaccio Mariarita, Salerno Paolo, Calice Giovanni, Laurino Simona, Russi Sabino, De Stefano Cristofaro, Maiello Monica, Merla Giuseppe, Falco Geppino, Mazzone Pellegrino
Biogem scarl, Istituto di Ricerche Genetiche 'Gaetano Salvatore', Ariano Irpino, Avellino, 83031, Italy.
CaWUR srl 83031 Ariano Irpino, Avellino, Italy.
Cell Commun Signal. 2025 Jul 1;23(1):320. doi: 10.1186/s12964-025-02329-2.
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.
胃癌（GC）是一种在未来几年发病率和死亡率都呈上升趋势的肿瘤。目前，这种恶性肿瘤的治疗方法包括手术联合铂类化合物或5-氟尿嘧啶卡培他滨给药。识别与胃癌进展相关的新型生物标志物是重新调整药物治疗以获得更有效患者反应的关键。在本研究中，我们报告激素上调的神经肿瘤相关激酶（HUNK）通过调节细胞稳态促进胃癌进展。特别是，我们证明HUNK通过与p38丝裂原活化蛋白激酶结合并使其磷酸化来促进胃癌细胞增殖，并且其缺失与胃癌细胞和患者来源的类器官的存活率降低有关。此外，我们报告HUNK正向调节MUC16/CA-125的表达，MUC16/CA-125是一种著名的癌症预后标志物。我们的研究结果首次揭示了HUNK在胃癌细胞中调节的分子机制，使这种激酶成为新型靶向治疗策略的有希望的候选者。
