Inositol monophosphatase 1 (IMPA1) promotes triple‐negative breast cancer progression through regulating mTOR pathway and EMT process

• Published in: Cancer medicine (Malden, MA) MA), 2023-01, Vol.12 (2), p.1602-1615
• Main Authors: Yang, Shao‐Ying, Xie, Yi‐Fan, Zhang, Tai‐Mei, Deng, Ling, Liao, Li, Hu, Shu‐Yuan, Zhang, Yin‐Ling, Zhang, Fang‐Lin, Li, Da‐Qiang
• Format: Article
• Language: English
• Subjects: Antibodies; Breast cancer; Cell adhesion & migration; Cell growth; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation; Cloning; Epidermal growth factor; Epithelial-Mesenchymal Transition - genetics; Gene expression; Gene Expression Regulation, Neoplastic; Humans; IMPA1; Kinases; Medical research; Mesenchyme; Metastases; Metastasis; myo-Inositol-1 (or 4)-monophosphatase; Neurogenesis; Plasmids; Proteins; Surgery; TNBC; TOR protein; TOR Serine-Threonine Kinases - metabolism; Transcriptomes; Triple Negative Breast Neoplasms - pathology; tumor growth; Tumorigenicity
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.4970

Triple‐negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, which is characterized by high heterogeneity and metabolic dysregulation. Inositol monophosphatase 1(IMPA1) is critical for the metabolism of inositol, which has profound effects on gene expression and other biological processes. Here, we report for the first time that IMPA1 was upregulated in TNBC cell lines and tissues, and enhanced cell colony formation and proliferation in vitro and tumorigenicity in vivo. Additionally, IMPA1 promoted cell motility in vitro and metastatic lung colonization in vivo. Mechanistic investigations by transcriptome sequencing revealed that 4782 genes were differentially expressed between cells with IMPA1 knockdown and control cells. Among the differentially expressed genes after IMPA1 knockdown, five significantly altered genes were verified via qRT‐PCR assays. Morerover, we found that the expression profile of those five targets as a gene set was significantly associated with IMPA1 status in TNBC cells. As this gene set was associated with mTOR pathway and epithelial‐mesenchymal transition (EMT) process, we further confirmed that IMPA1 induced mTOR activity and EMT process, which at least in part contributed to IMPA1‐induced TNBC progression. Collectively, our findings reveal a previously unrecognized role of IMPA1 in TNBC progression and identify IMPA1 as a potential target for TNBC therapy. IMPA1 was upregulated in TNBC tissues, and enhanced cell proliferation and metastatic potential. Five downstream targets of IMPA1 were identified, which are invovled in mTOR pahtway and EMT process to drive TNBC progression.