Small leucine zipper protein functions as a modulator for metabolic reprogramming of colorectal cancer cells by inducing nutrient stress-mediated autophagy

Suhyun Kim, Minseok Oh, Minsoo Kang, Jesang Ko

    Research output: Contribution to journalArticlepeer-review

    3 Citations (Scopus)

    Abstract

    In multiple cancers, autophagy promotes tumor development by recycling intracellular components into metabolic pathways. Autophagy-induced metabolic reprogramming and plasticity lead to cancer cell survival and resistance to anticancer therapy. We investigated the role of small leucine zipper protein (sLZIP) in autophagy and cell survival under nutrient-deficient conditions in colorectal cancer (CRC). sLZIP was induced by nutrient stress and increased the transcription of microtubule-associated protein 1A/1B-light chain 3 (LC3), by directly binding to its promoter. Under nutrient stress conditions, sLZIP activated autophagy and promoted the survival of CRC cells. sLZIP induced metabolic reprogramming of CRC cells, to activate glutaminolysis and the tricarboxylic acid cycle. sLZIP also enhanced the autophagic degradation of Keap1 and the nuclear accumulation of Nrf2, leading to NQO1 expression, for maintenance of redox homeostasis. sLZIP-knockout CRC cells exhibited impaired autophagy induction in the glycolytic inhibition state. Xenograft mice lacking sLZIP showed decreased tumor growth, by rendering CRC cells sensitive to glycolysis inhibition. The expression of sLZIP and LC3B was highly elevated in tumors of CRC patients compared to that in normal tissues, and correlated with the progression of CRC. These findings suggest that sLZIP drives autophagy and metabolic reprogramming to promote colorectal tumorigenesis.

    Original languageEnglish
    Article number505
    JournalCellular and Molecular Life Sciences
    Volume79
    Issue number9
    DOIs
    Publication statusPublished - 2022 Sept

    Bibliographical note

    Publisher Copyright:
    © 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.

    Keywords

    • Autophagy
    • Colorectal cancer
    • Metabolic reprogramming
    • Transcriptional regulation

    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology
    • Pharmacology
    • Cellular and Molecular Neuroscience
    • Cell Biology

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