Related Experiment Video

Updated: May 26, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Neutral Sphingomyelinase-2 Restrains TAZ to Suppress Breast Tumor Growth

Andrew E Resnick, Victoria Franzi, Botheina K Ghandour

    Biorxiv : the Preprint Server for Biology
    |May 25, 2026
    PubMed

    Insights

    Restoring neutral sphingomyelinase-2 (nSMase2) activity, which produces ceramide (Cer), can suppress breast cancer growth. This metabolic pathway highlights a new therapeutic strategy by targeting ceramide signaling.

    Area of Science:

    • Oncology
    • Metabolic Signaling
    • Molecular Biology

    Background:

    • Loss of tumor suppressor gene (TSG) activity is common in cancers, leading to poor outcomes.
    • Therapeutic restoration of TSGs remains a significant challenge in cancer treatment.
    • Metabolic signaling pathways offer a potential strategy for enforcing tumor suppressive programs.

    Purpose of the Study:

    • To identify novel mediators of ceramide (Cer)-dependent tumor suppression.
    • To investigate the role of neutral sphingomyelinase-2 (nSMase2) in breast cancer (BC).
    • To explore nSMase2-Cer signaling as a potential therapeutic target.

    Main Methods:

    • Investigated the role of neutral sphingomyelinase-2 (nSMase2) in ceramide (Cer) metabolism.
    • Assessed nSMase2 expression in breast cancer (BC) tissues.
    • Evaluated the impact of nSMase2 restoration on tumor growth, anchorage-independent growth (AIG), and HIPPO pathway signaling (TAZ and YAP).

    Main Results:

    • Identified neutral sphingomyelinase-2 (nSMase2) as a key mediator of ceramide (Cer)-dependent tumor suppression.
    • Found that nSMase2 is frequently suppressed in breast cancer (BC).
    • Demonstrated that nSMase2 restoration inhibits tumorigenesis by suppressing anchorage-independent growth (AIG) and restraining the HIPPO pathway effector TAZ.

    Conclusions:

    • Defined a novel metabolic tumor suppressor pathway involving nSMase2 and ceramide (Cer).
    • Clarified the roles of sphingolipid (SL) metabolism and HIPPO signaling in cancer.
    • Highlighted the potential of reactivating nSMase2-Cer signaling as a therapeutic strategy for breast cancer (BC).

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