Aberrant expression of GOLM1 protects ALK+ anaplastic large cell lymphoma from apoptosis by enhancing BCL-XL stability.

TitleAberrant expression of GOLM1 protects ALK+ anaplastic large cell lymphoma from apoptosis by enhancing BCL-XL stability.
Publication TypeJournal Article
Year of Publication2023
AuthorsZi Z, Du S, Zhang L, Wang Y, Ding L, Zhang C, Wang H, Pawlicki J, Cai Y, Yao Y, Zhou F, Tong Y, Riley JL, Cai Q, Ma X, Wei F
JournalBlood Adv
Volume7
Issue15
Pagination4049-4063
Date Published2023 Aug 08
ISSN2473-9537
KeywordsAnaplastic Lymphoma Kinase, Animals, Cell Line, Tumor, Humans, Lymphoma, Large-Cell, Anaplastic, Membrane Proteins, Mice, Receptor Protein-Tyrosine Kinases, Staurosporine
Abstract

Golgi membrane protein 1 (GOLM1) is aberrantly expressed in many types of solid tumors and contributes to cancer development; however, its role in hematopoietic and lymphoid neoplasms remains unknown. Here, we report that GOLM1 was significantly upregulated in anaplastic large cell lymphoma (ALCL), particularly in anaplastic lymphoma kinase-positive (ALK+) ALCL. Mechanistically, the expression of GOLM1 was induced by nucleophosmin-ALK in both ALK-transformed T cells and ALCL cell lines through AKT/mTOR pathway. Knockdown of GOLM1 expression led to a reduction in the growth and viability of ALCL cells with increased spontaneous apoptosis, whereas ectopic expression of GOLM1 protected ALCL cells from apoptosis induced by staurosporine treatment. Moreover, GOLM1 directly interacted with B-cell lymphoma-extra large protein (a crucial anti-apoptosis regulator) and significantly prolonged its stability. Introduction of GOLM1 promoted ALK+ ALCL cells colony formation in vitro and tumor growth in a murine xenograft model. Taken together, our findings demonstrate, to our knowledge, for the first time that GOLM1 plays a critical role in suppressing apoptosis and promoting the progression of ALK+ ALCL and provide evidence that GOLM1 is a potential biomarker and therapeutic target in ALK-induced hematological malignancies.

DOI10.1182/bloodadvances.2022008384
Alternate JournalBlood Adv
PubMed ID36763539
PubMed Central IDPMC10388734

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