Aberrant ENPP2 expression promotes tumor progression in multiple myeloma

Li, Yuxiang; Zhang, Lin; Zhao, Xia; Jiang, Xiaona; Xiao, Fengjun; Sun, Huiyan; Wang, Lisheng

doi:10.1080/10428194.2021.2010055

Cited by 3 publications

(1 citation statement)

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“…ENPP2 expression is upregulated in corpulence patients and mice and is associated with insulin resistance and impaired glucose tolerance [11,12]. ENPP2 has been described to be engaged in several solid neoplasms, such as chondrosarcoma [13], breast cancer [14], hepatocellular carcinoma [15], and pancreatic cancer [16], and has been mentioned in multiple myeloma [17]. Nevertheless, the effects of ENPP2 inhibition in CLL remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

ENPP2 promotes progression and lipid accumulation via AMPK/SREBP1/FAS pathway in chronic lymphocytic leukemia

Wang,

Lu,

et al. 2023

Preprint

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Disorders of lipid metabolism are critical factors in the progression of chronic lymphocytic leukemia (CLL). The characteristics of lipid metabolism and related regulatory mechanisms of CLL remain unclear. Hence, we identified altered metabolites in CLL patients by lipidomic to investigate aberrant lipid metabolism pathways. Based on the area under the curve value, a combination of three metabolites (PC O-24:2_18:2, PC O-35:3, and LPC 34:3) potentially served as a biomarker for the diagnosis of CLL. Moreover, utilizing integrated lipidomic, transcriptomic, and molecular studies, we reveal that ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) plays a crucial role in regulating oncogenic lipogenesis. ENPP2 expression was significantly elevated in CLL patients compared to normal cells and was validated in an independent cohort. Besides, ENPP2 knockdown and targeted inhibitor PF-8380 treatment exerted an anti-tumor effect by regulating cell viability, proliferation, apoptosis, cell cycle, and enhanced the drug sensitivity to ibrutinib. Mechanistically, ENPP2 inhibited AMP-activated protein kinase (AMPK) phosphorylation and promoted lipogenesis through the sterol regulatory element-binding transcription factor 1 (SREBP-1)/fatty acid synthase (FAS) signaling pathway to promote lipogenesis. Taken together, our findings unravel the lipid metabolism characteristics of CLL, and highlight the potential role of ENPP2 as a novel therapeutic target for CLL treatment.

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