Harnessing the polyamine transport system to treat BRAF inhibitor-resistant melanoma

Alexander, Eric T.; Naggar, Olivia El; Fahey, Erin; Mariner, Kelsey; Donnelly, Julia; Wolfgang, Katelyn; Phanstiel, Otto; Gilmour, Susan K.

doi:10.1080/15384047.2021.1883185

Cited by 10 publications

(6 citation statements)

References 55 publications

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“…Drugs or polyamine analogs targeting polyamin zymes associated with polyamine metabolism are effective against cancer i animal models, and some of them have been evaluated in clinical trials. H are still some problematic areas that need to be addressed, and the specifi by which polyamine metabolism affects HCC are still unclear; in this pap Preclinical use [124,125] The potential of PBT to enhance anti-tumor immune responses is consistent with recent studies using bone marrow-specific knockout ODC. ODC activity and polyamines favored tumor-resistant M2-type macrophage polarization while decreasing anti-tumor-resistant M1-type macrophage polarization.…”

Section: Discussionmentioning

confidence: 53%

Polyamine Signal through HCC Microenvironment: A Key Regulator of Mitochondrial Preservation and Turnover in TAMs

Liu,

Yan,

et al. 2024

IJMS

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Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and, with increasing research on the tumor immune microenvironment (TIME), the immunosuppressive micro-environment of HCC hampers further application of immunotherapy, even though immunotherapy can provide survival benefits to patients with advanced liver cancer. Current studies suggest that polyamine metabolism is not only a key metabolic pathway for the formation of immunosuppressive phenotypes in tumor-associated macrophages (TAMs), but it is also profoundly involved in mitochondrial quality control signaling and the energy metabolism regulation process, so it is particularly important to further investigate the role of polyamine metabolism in the tumor microenvironment (TME). In this review, by summarizing the current research progress of key enzymes and substrates of the polyamine metabolic pathway in regulating TAMs and T cells, we propose that polyamine biosynthesis can intervene in the process of mitochondrial energy metabolism by affecting mitochondrial autophagy, which, in turn, regulates macrophage polarization and T cell differentiation. Polyamine metabolism may be a key target for the interactive dialog between HCC cells and immune cells such as TAMs, so interfering with polyamine metabolism may become an important entry point to break intercellular communication, providing new research space for developing polyamine metabolism-based therapy for HCC.

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Section: Discussionmentioning

confidence: 53%

Polyamine Signal through HCC Microenvironment: A Key Regulator of Mitochondrial Preservation and Turnover in TAMs

Liu,

Yan,

et al. 2024

IJMS

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“…Cells were also treated with Trimer44NMe, a polyamine transport inhibitor (PTI) often used in conjunction with DFMO in polyamine-blocking strategies ( 22 , 23 , 24 , 25 ), to determine its ability to block the import of acetylated spermidine. In both HCT116 and HeLa cells, adding the PTI prevented the uptake of N 8 -AcSpd, as evidenced by the lack of its conversion to spermidine as well as the absence of N 8 -AcSpd accumulation in the presence of the HDAC10 inhibitor ( Figs.…”

Section: Resultsmentioning

confidence: 99%

Histone deacetylase-10 liberates spermidine to support polyamine homeostasis and tumor cell growth

Stewart¹,

Foley²,

Holbert³

et al. 2022

Journal of Biological Chemistry

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“…Abnormal regulation of polyamine metabolism appears to be captured in various human diseases [ 4 , 5 ], notably malignant neoplasms [ 6 ]. To maintain continual proliferation, cancer cells require sustained and elevated intracellular polyamine pools, which is directly linked to oncogenes, including MYC , JUN , FOS , KRAS and BRAF [ 5 , 7 ]. Furthermore, emerging data showing that polyamines also have anti-inflammatory and immunosuppressive properties in the tumor microenvironment (TME) [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Antizyme inhibitor family: biological and translational research implications

Feng,

Wang,

Shao

et al. 2024

Cell Commun Signal

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Metabolism of polyamines is of critical importance to physiological processes. Ornithine decarboxylase (ODC) antizyme inhibitors (AZINs) are capable of interacting with antizymes (AZs), thereby releasing ODC from ODC-AZs complex, and promote polyamine biosynthesis. AZINs regulate reproduction, embryonic development, fibrogenesis and tumorigenesis through polyamine and other signaling pathways. Dysregulation of AZINs has involved in multiple human diseases, especially malignant tumors. Adenosine-to-inosine (A-to-I) RNA editing is the most common type of post-transcriptional nucleotide modification in humans. Additionally, the high frequencies of RNA-edited AZIN1 in human cancers correlates with increase of cancer cell proliferation, enhancement of cancer cell stemness, and promotion of tumor angiogenesis. In this review, we summarize the current knowledge on the various contribution of AZINs related with potential cancer promotion, cancer stemness, microenvironment and RNA modification, especially underlying molecular mechanisms, and furthermore explored its promising implication for cancer diagnosis and treatment.

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Harnessing the polyamine transport system to treat BRAF inhibitor-resistant melanoma

Cited by 10 publications

References 55 publications

Polyamine Signal through HCC Microenvironment: A Key Regulator of Mitochondrial Preservation and Turnover in TAMs

Polyamine Signal through HCC Microenvironment: A Key Regulator of Mitochondrial Preservation and Turnover in TAMs

Histone deacetylase-10 liberates spermidine to support polyamine homeostasis and tumor cell growth

Antizyme inhibitor family: biological and translational research implications

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