Ask about this productRelated genes to: PLD2 Blocking Peptide
- Gene:
- PLD2 NIH gene
- Name:
- phospholipase D2
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 17p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1998-08-21
- Date modifiied:
- 2016-10-05
Related products to: PLD2 Blocking Peptide
Related articles to: PLD2 Blocking Peptide
- Tumor cells shape the immunosuppressive tumor microenvironment (TME) through coordinated interactions with tumor-associated macrophages (TAMs), regulatory T cells (T), immune checkpoint pathways and suppressive cytokines, thereby limiting the efficacy of immunotherapy across diverse cancer types. Phospholipase D (PLD) enzymes, particularly the PLD1 and PLD2 isoforms, have been implicated in oncogenic signaling and tumor progression; however, their tumor-intrinsic roles in modulating the immune landscape remain largely undefined. Here we demonstrated that both genetic ablation and pharmacological inhibition of PLD1 and PLD2 reprogram the TME and enhance antitumor immunity in a syngeneic melanoma model. Elevated PLD expression is associated with increased infiltration of M2-like TAMs, decreased 'eat me' signals and enhanced 'don't eat me' signals. Conversely, loss or inhibition of PLD1 and PLD2 reduced T recruitment and enhanced infiltration of Th1, Th17 and cytotoxic CD8⁺ T cells, accompanied by downregulation of immune checkpoint molecules and restoration of T cell effector function. Depletion studies revealed that PLD-driven TAM polarization critically impairs CD8⁺ T cell-mediated antitumor responses. Mechanistically, PLD1 and PLD2 enhance CCL19 secretion, promote macrophage polarization toward an immunosuppressive phenotype and induce programmed death-ligand 1 (PD-L1) expression by activating the PI3K-Akt-NF-κB signaling axis, thereby promoting tumor immune evasion. Notably, PLD inhibition reduced CCL19 production, abrogated IFN-γ- or CCL19-induced PD-L1 expression, decreased TAM infiltration and increased CD8⁺ T cell infiltration, collectively shifting the TME toward an immune-activated state. These findings suggest that tumor-intrinsic PLD1 and PLD2 function as modulators of immune suppression and that PLD inhibition represents a promising strategy to overcome resistance to cancer immunotherapy. - Source: PubMed
Publication date: 2026/06/04
Lee HyesungLim Seong HunHwang Won ChanKim Tae HyunBae KyeongseokLee JinuMin Do Sik - Gynecologic cancers (GCs), including ovarian, cervical, and endometrial cancers, represent a substantial global health burden, characterized by high rates of recurrence, therapeutic resistance, and metastatic dissemination. Tumor dormancy-a state in which disseminated tumor cells (DTCs) persist in a non-proliferative, quiescent phase, thereby evading conventional therapies and immune surveillance-constitutes a critical yet often underestimated driver of these clinical challenges. This comprehensive review systematically integrates the multifaceted roles and current research landscape of dormant tumor cells in gynecologic malignancies. The core innovation lies in a three-level analytical framework that examines dormancy through intrinsic molecular switches, extrinsic microenvironmental remodeling, and cross-cancer type comparisons. Specifically, the mechanisms governing dormancy initiation, maintenance, and reactivation are delineated for cervical, ovarian, and endometrial cancers. Several key conclusions emerge from this synthesis. Common regulatory hubs across gynecologic cancers include hypoxic conditions, cell-cycle regulators such as the DREAM complex, stemness-associated pathways exemplified by the HIF-1α/PLD2 axis, and stromal cell interactions, notably cancer-associated fibroblast-extracellular matrix crosstalk. Dormant cells further orchestrate sophisticated immune evasion strategies, including downregulation of major histocompatibility complex class I and upregulation of immune checkpoint molecules, thereby establishing a reservoir of drug-tolerant persister cells that drive post-treatment relapse and acquired resistance. Notably, substantial heterogeneity exists across different gynecologic cancer types: ovarian cancer engages the most diverse repertoire of dormancy-related pathways, while uterine sarcoma remains a conspicuous research gap. Collectively, this review establishes the dormant tumor cell reservoir as a promising therapeutic target to prevent recurrence and overcome therapy resistance. Specific actionable targets-including Dyrk1A, PLD2, LATS1/2, and Egfl6-are proposed, providing a theoretical foundation for the development of novel diagnostic tools and therapeutic strategies aimed at improving long-term outcomes for patients with gynecologic malignancies. - Source: PubMed
Publication date: 2026/05/15
Fu AizhenMa ZhenZou KaiWu FeiyuanZou Xinxin - The tumor microenvironment, including extracellular pH (pH), has emerged as a key regulator of tumor cellular function. Although extracellular acidification sensing and function are well established, the effect of extracellular alkalinization on cellular functioning remains unclear. Here, we report that transient receptor potential ankyrin 1 (TRPA1) functions as an alkaline sensor and mediator of cell death in melanoma cells. Exposure to alkaline pH (8.1) or allyl isothiocyanate (AITC), a TRPA1 agonist, significantly reduced melanoma cell viability. We found that cell death was propidium iodide-positive and annexin V-negative, suggesting that pH or AITC treatment induced necrosis rather than apoptosis. TRPA1 activation induced sustained Ca influx, which was suppressed by either extracellular Ca removal or treatment with the TRPA1 inhibitor, HC-030031, both of which attenuated cell death. Pharmacological screening has identified phosphatidylcholine-specific phospholipase D1 (PLD1) as a positive regulator of cell death. We confirmed that transfection with PLD1 siRNA significantly reduced AITC-induced cell death, whereas PLD2, PLD3, and NAPE-PLD siRNAs had no effect. These observations suggest that the vulnerability of melanoma cells to alkaline pH is mediated by activation of the TRPA1-PLD1 axis. Thus, TRPA1 and PLD1 are potential targets for therapeutic intervention in melanoma. - Source: PubMed
Publication date: 2026/04/23
Nakano ReiKuji ManamiSugimura ManaYachiku NaoyaKitanaka NanakoKitanaka TakuSuwabe YokoNaruke AtsutoNunomura JunichiUechi MasamiNakayama TomohiroSugiya Hiroshi - Progression through the cell cycle requires coordinated regulation of transcription, chromatin state, and cellular metabolism. While metabolic enzymes are known to localize the nucleus and influence chromatin states, how nuclear metabolism itself oscillates during the cell cycle remains unexplored. Here, we combine a customized FUCCI-3 reporter with chromatome mass spectrometry and high-throughput imaging to systematically resolve nuclear and chromatin-associated metabolic changes across cell cycle phases. We identify phosphatidylinositol metabolism as a nuclear pathway that oscillates with the cell cycle, with PIP5K1A, PLCD3, and PLD2 showing phase-specific nuclear and chromatin dynamics. Nuclear PIP2 levels redistribute within the nucleus depending on cell cycle stage. Downregulation of PIP5K1A reduces nuclear PIP2 levels, whereas nuclear enrichment of PIP5K1A increases PIP2 abundance in the nucleus and nucleolus, functionally linking PIP5K1A nuclear localization to nuclear PIP2 synthesis. Moreover, perturbation of nuclear PIP2 synthesis alters chromatin methylation, with a pronounced impact on H4K20 monomethylation. Together, our results reveal that nuclear phosphatidylinositol metabolism is cell cycle regulated and functionally linked to chromatin methylation, establishing nuclear lipid metabolism as a previously unrecognized layer of cell cycle control. - Source: PubMed
Publication date: 2026/04/21
Gañez-Zapater AntoniKourtis SavvasElbæk Camilla ReiterEspinar LorenaToro-Márquez CarolinaColl-Manzano AlbertSmiriglia AlfredoGarcía-López LauraWiegand LauraGuirola MariaFontaine FrédéricMorandi AndreaMüller André CSdelci Sara - - Source: PubMed
Publication date: 2026/03/06
Wang QingzhuTong YannaDing YuchuanWeiss AlexanderFayyaz Aminah IGeng Xiaokun