American Association for Cancer Research
00085472can163011-sup-174168_2_supp_4061005_jqh93n.xlsx (11.95 kB)

Supplementary table 5 from Loss of FAM46C Promotes Cell Survival in Myeloma

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posted on 2023-03-31, 00:46 authored by Yuan Xiao Zhu, Chang-Xin Shi, Laura A. Bruins, Patrick Jedlowski, Xuewei Wang, K. Martin Kortüm, Moulun Luo, Jonathan M. Ahmann, Esteban Braggio, A. Keith Stewart

Pathway analysis of the genes differeentially expressed in OCIMY5 cell after depletion of FAM46C. The genes were determined as differentially expressed were submitted to Ingenuity Pathway Analysis (IPA, for pathway enrichment analysis. The results of top twenty four pathways affected were shown.


Mayo Clinic

National Institutes of Health



FAM46C is one of the most recurrently mutated genes in multiple myeloma; however its role in disease pathogenesis has not been determined. Here we demonstrate that wild-type (WT) FAM46C overexpression induces substantial cytotoxicity in multiple myeloma cells. In contrast, FAM46C mutations found in multiple myeloma patients abrogate this cytotoxicity, indicating a survival advantage conferred by the FAM46C mutant phenotype. WT FAM46C overexpression downregulated IRF4, CEBPB, and MYC and upregulated immunoglobulin (Ig) light chain and HSPA5/BIP. Furthermore, pathway analysis suggests that enforced FAM46C expression activated the unfolded protein response pathway and induced mitochondrial dysfunction. CRISPR-mediated depletion of endogenous FAM46C enhanced multiple myeloma cell growth, decreased Ig light chain and HSPA5/BIP expression, activated ERK and antiapoptotic signaling, and conferred relative resistance to dexamethasone and lenalidomide treatments. Genes altered in FAM46C-depleted cells were enriched for signaling pathways regulating estrogen, glucocorticoid, B-cell receptor signaling, and ATM signaling. Together these results implicate FAM46C in myeloma cell growth and survival and identify FAM46C mutation as a contributor to myeloma pathogenesis and disease progression via perturbation in plasma cell differentiation and endoplasmic reticulum homeostasis. Cancer Res; 77(16); 4317–27. ©2017 AACR.

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