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

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

  • Cell Commun Signal. 2025 Jul 1;23(1):320. doi: 10.1186/s12964-025-02329-2.
Giuseppina di Paola # 1 2,  Francesco Albano # 3,  Pietro Zoppoli 4,  Daniele Bravoco 1 5,  Teresa D'Amore 6,  Elena Amendola 3 7,  Valeria Lucci 3,  Luca Roberto 1,  Mariarita Brancaccio 3,  Paolo Salerno 8,  Giovanni Calice 6,  Simona Laurino 6,  Sabino Russi 6,  Cristofaro De Stefano 9,  Monica Maiello 9,  Giuseppe Merla 8 10,  Geppino Falco # 11 12,  Pellegrino Mazzone # 13 14
Affiliations

Affiliations

  • 1 Biogem scarl, Istituto di Ricerche Genetiche 'Gaetano Salvatore', Ariano Irpino, Avellino, 83031, Italy.
  • 2 CaWUR srl 83031 Ariano Irpino, Avellino, Italy.
  • 3 Department of Biology, University of Naples Federico II, Naples, 80147, Italy.
  • 4 Department of Molecular Medicine and Health Biotechnology, University di Napoli Federico II, Naples, 80131, Italy.
  • 5 Department of Public Health, Federico II University of Naples, Naples, 80131, Italy.
  • 6 IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Potenza, Italy.
  • 7 Istituto degli Endotipi in Oncologia, Metabolismo e Immunologia "G. Salvatore" (CNR-EOMI) Consiglio Nazionale delle Ricerche (CNR), Naples, Italy.
  • 8 Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, 80138, Italy.
  • 9 U.O.C Reproduction Physiology Unit, San Giuseppe Moscati, Avellino, 83100, Italy.
  • 10 Laboratory of Regulatory and Functional Genomics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, 71013, Italy.
  • 11 Biogem scarl, Istituto di Ricerche Genetiche 'Gaetano Salvatore', Ariano Irpino, Avellino, 83031, Italy. geppino.falco@unina.it.
  • 12 Department of Biology, University of Naples Federico II, Naples, 80147, Italy. geppino.falco@unina.it.
  • 13 Biogem scarl, Istituto di Ricerche Genetiche 'Gaetano Salvatore', Ariano Irpino, Avellino, 83031, Italy. pellegrino.mazzone@biogem.it.
  • 14 CaWUR srl 83031 Ariano Irpino, Avellino, Italy. pellegrino.mazzone@biogem.it.
  • # Contributed equally.
PMID: 40598530 DOI: 10.1186/s12964-025-02329-2
Abstract

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.

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