bims-prolim 2025-07-20 papers

bims-prolim

Biomed News

on Protein lipidation, metabolism and cancer

Issue of 2025–07–20
six papers selected by
Bruna Martins Garcia, CABIMER

S-palmitoylation: a novel insight in the development and immunotherapy of oral squamous cell carcinoma.
Lenvatinib promotes hepatocellular carcinoma pyroptosis by regulating GSDME palmitoylation.
Lactate and lactylation in breast cancer: current understanding and therapeutic opportunities.
Shedding of GPP130 by PC7 and Furin: Potential Implication in Lung Cancer Progression.
Altered glycosylation of EVs in cancers: galectin-3-binding protein (LGALS3BP).
Palmitoylation by ZDHHC family members regulate B-cell lymphoma growth.

J Cancer. 2025 ;16(9): 2787-2799

S-palmitoylation: a novel insight in the development and immunotherapy of oral squamous cell carcinoma.

Xue-Ting Yuan, Jing-Ru Wang, Ying Yang, Jian-Gang Ren.

  S-palmitoylation (hereinafter referred to as palmitoylation) is a reversible lipid modification that has recently received considerable attention in cancer research. Despite its known association with tumour progression and treatment response, it remains unclear how palmitoylation could be targeted for enhancing therapeutic outcomes in oral squamous cell carcinoma (OSCC). This review summarises palmitoylated proteins common in various cancers and highlights emerging targets specific to OSCC, emphasising their roles in protein stability, signalling pathways, and cellular behaviour. Additionally, we explore new trends in targeting palmitoylated proteins to manage cancer progression and bolster the immune response in OSCC. Furthermore, this review highlights existing knowledge gaps and calls for detailed investigations into OSCC-specific palmitoylation mechanisms, including the expression levels of palmitoylated proteins and palmitoylation enzymes and their effect on OSCC signalling pathways.

Keywords:  OSCC; immunotherapy; palmitoylation; palmitoyltransferase; signaling pathway

DOI:  https://doi.org/10.7150/jca.110721
Cancer Biol Ther. 2025 Dec;26(1): 2532217

Lenvatinib promotes hepatocellular carcinoma pyroptosis by regulating GSDME palmitoylation.

Yuan Yuan, Mu-Ru Wang, Yang Ding, Ya Lin, Ting-Ting Xu, Xing-Xing He, Pei-Yuan Li.

  Lenvatinib, as a multi-kinase inhibitor, has been approved as a first-line drug for patients with advanced hepatocellular carcinoma (HCC). Gasdermin E (GSDME)-mediated pyroptosis, a form of programmed cell death, can be induced by chemotherapy drugs or certain kinase inhibitors. However, the role of Lenvatinib in inducing pyroptosis in HCC warrants further investigation. Phase contrast microscopy, LDH assays, and gain- and loss-of-function strategies were used to evaluate Lenvatinib-induced pyroptosis in HCC cells. GSDME palmitoylation was assessed via the acyl-biotin exchange method. In vivo, a subcutaneous HCC xenograft model in nude mice were established to assess the effects of interfering with GSDME on the sensitivity of HCC to Lenvatinib. Lenvatinib induced pyroptosis in HCC cells in a dose- and time-dependent manner. Additionally, Lenvatinib promoted GSDME cleavage, with upregulation of GSDME enhancing pyroptosis and downregulation reducing this effect. The ABE method revealed that GSDME is palmitoylated, and Lenvatinib increased its palmitoylation, promoting plasma membrane localization and enhancing protein stability. Inhibition of GSDME palmitoylation by 2-BP blocked Lenvatinib-induced pyroptosis. In vivo, upregulation of GSDME increased HCC sensitivity to Lenvatinib and inhibited tumor growth. Lenvatinib induces pyroptosis in HCC by promoting the palmitoylation of GSDME, enhancing its localization to the plasma membrane and increasing its protein stability. Interfering with GSDME, both in vitro and in vivo, affects Lenvatinib-induced pyroptosis, thereby altering the therapeutic sensitivity of HCC to Lenvatinib. Targeting GSDME palmitoylation represents a potential therapeutic strategy for HCC, as it enhances Lenvatinib-induced pyroptosis and improves the therapeutic response.

Keywords:  GSDME; Hepatocellular carcinoma; Lenvatinib; palmitoylation; pyroptosis

DOI:  https://doi.org/10.1080/15384047.2025.2532217
Cancer Biol Med. 2025 Jul 16. pii: j.issn.2095-3941.2025.0173. [Epub ahead of print]

Lactate and lactylation in breast cancer: current understanding and therapeutic opportunities.

Lan Huang, Xuemei Chen, Meina Yan, Ze Xiang, Jian Wu.

  Breast cancer (BC) has the highest prevalence among cancers specific to women, and its incidence rates are increasing in many countries. Subtypes of BC, including HER2-positive or triple-negative BC, exhibit differing treatment responses; consequently, demand for personalized therapy is increasing, and relevant precision medicine strategies are under development. Aerobic glycolysis in cancer cells can lead to excessive lactate production, which in turn promotes lactylation and influences tumor cell behavior. Epigenetic alterations and metabolic reprogramming are prominent characteristics of tumors. Because lactate and lactylation are important in cancer, further investigation of the mechanisms underlying lactate metabolism and lactylation, and the development of therapeutic strategies targeting these processes, are topics of increasing interest. This review describes current research on lactate metabolism and lactylation in BC, thus offering new perspectives for advancing treatment and management toward more precise and personalized approaches that will ultimately increase BC survival rates and patient quality of life.

Keywords:  Lactate; breast cancer; immunotherapy prognosis; lactylation; tumor metabolism

DOI:  https://doi.org/10.20892/j.issn.2095-3941.2025.0173
Int J Mol Sci. 2025 Jun 26. pii: 6164. [Epub ahead of print]26(13):

Shedding of GPP130 by PC7 and Furin: Potential Implication in Lung Cancer Progression.

Priyanka Prabhala, Stephanie Duval, Alexandra Evagelidis, Maïlys Le Dévéhat, Vatsal Sachan, Nabil G Seidah.

  From a previously performed proteomics screen, GPP130, or Golgi phosphoprotein of 130 kDa, was identified as a potential substrate of the proprotein convertase 7 (PC7; PCSK7). GPP130 is a type-II transmembrane protein with a luminal domain containing endosomal and Golgi-retrieval determinants, enabling a unique trafficking route. Most of the previous work on GPP130 relates to its binding and retrograde trafficking of the Shiga toxin. However, its cellular biology and its biochemical characterization remain understudied. Recently, GPP130 was reported to be implicated in cell cycle progression and cell proliferation in head and neck cancer cells. This led us to analyze the cBioPortal for Cancer Genomics, revealing that the GPP130/GOLIM4 gene is amplified in many cancers, including lung, ovarian, and cervical. This observation led us to use the A549 lung cancer cell line to investigate the growth-regulating roles of endogenous and overexpressed GPP130 and to analyze the impact of its cleavage/shedding by PC7 and/or Furin on cellular growth. Our cell-based assays suggest that GPP130 is a novel pro-protein convertase substrate that increases cell proliferation in A549, SKOV3, and HeLa cells, and that the latter activity is enhanced following its cleavage by PC7 and/or Furin into a membrane-bound N-terminal product and secreted C-terminal fragments. This novel work sheds light on the cell biology of the poorly characterized GPP130, its proliferative activity, and modulation upon its shedding by PC7 and Furin in lung cancer progression.

Keywords:  Cys-palmitoylation; GOLIM4 proprotein convertases; GPP130; PC7; furin; lung cancer; post-translational modifications; proteolysis

DOI:  https://doi.org/10.3390/ijms26136164
Discov Oncol. 2025 Jul 15. 16(1): 1336

Altered glycosylation of EVs in cancers: galectin-3-binding protein (LGALS3BP).

Jie-Yi Koh Kok, Bey-Hing Goh, Wai-Leng Lee.

   INTRODUCTION: Extracellular vesicles (EVs) are membrane-bound structures secreted by various cell types, acting as carriers of complex cargos that facilitate intercellular communication. Their presence in biofluids highlights their potential for disease biomarker identification. Glycans, crucial components of EVs, undergo glycosylation, a key post-translational modification (PTM) involved in many biological processes. Aberrant glycosylation is linked to disease, particularly cancer.
AREAS COVERED: This review examines alterations in EV glycosylation patterns in cancer and their biological implications. It synthesizes findings from cell studies and biofluid analyses (including blood and urine), emphasizing the potential of combined glycosylation profiles as circulating cancer detection. Key findings highlight the elevation of terminal sialic acid levels, dysregulation of N-glycan patterns, and the identification of galectin-3-binding protein (LGALS3BP) as a common pattern of altered glycosylated protein in cancer-derived EVs.
EXPERT OPINION/COMMENTARY: This review uniquely suggests a novel combination of the altered glycosylation pattern of cancer-derived EVs based on changes observed in current studies. By highlighting specific alterations that differentiate cancer-derived EVs from those of healthy origin, the analysis offers valuable insights into diagnostic and prognostic applications. These findings may facilitate the development of non-invasive biomarkers that enhance early cancer detection and monitoring.

Keywords:  Biomarkers; Cancer; Extracellular vesicles; Galectin-3 binding protein (LGALS3BP); Glycosylation

DOI:  https://doi.org/10.1007/s12672-025-03121-x
Int J Biol Macromol. 2025 Jul 09. pii: S0141-8130(25)06431-1. [Epub ahead of print]320(Pt 2): 145876

Palmitoylation by ZDHHC family members regulate B-cell lymphoma growth.

Yichen Liu, Shiyun Hu, Özlem Önder, Anagh Sahasrabuddhe, Ali Rajabi, Annika Seitz, Debora de Jong, Jasper Koerts, Lydia Visser, Agnieszka Dzikiewicz-Krawczyk, Megan S Lim, Kojo S Elenitoba-Johnson, Anke van den Berg, Lotteke J Y M Ziel-Swier, Joost Kluiver.

  The ZDHHC palmitoyl transferase family consists of 24 members, of which several have been linked to the development of cancer. We previously showed that inhibition of ZDHHC11 decreased growth of several B-cell lymphoma subtypes. In this study, we evaluated the effect of protein palmitoylation on the proteome in general and investigated expression and function of ZDHHC family members in a panel of Burkitt, Hodgkin and diffuse large B-cell lymphoma cell lines. Proteomic analysis of Burkitt lymphoma cells treated with the general palmitoylation inhibitor 2-bromopalmitate (2-BP) revealed 1089 differentially expressed proteins of which 124 were involved in cell cycle and apoptosis related gene ontologies. In line with this, 2-BP treatment resulted in an increased percentage of apoptotic cells in all three lymphoma subtypes. To allow a further selection of the most relevant family members of ZDHHC palmitoyl transferases, we studied expression patterns and assessed the dependency. The combined analyses revealed potential roles for ZDHHC11 and ZDHHC18 in the observed phenotype. Knockdown of ZDHHC18 in four Burkitt lymphoma cell lines revealed a decreased cell viability. This is the first study showing a critical role for palmitoylation in controlling growth of B-cell lymphoma. Moreover, we provide evidence that next to the previously identified ZDHHC11, ZDHHC18 is also crucial for B-cell lymphoma growth expanding the potential functional role for ZDHHC family members in lymphomagenesis.

Keywords:  2-bromopalmitate; B-cell lymphoma; Palmitoylation; ZDHHC family; ZDHHC11; ZDHHC18

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.145876