Subcutaneous Adipocytes Promote Melanoma Cell Growth by Activating the Akt Signaling Pathway

Kwan, Hiu Yee; Fu, Xiu‐Qiong; Liu, Bin; Chao, Xiaojuan; Chan, Chitat; Cao, Hongxin; Su, Tao; Tse, Anfernee Kai-Wing; Wang, Fong; Yu, Zhi‐Ling

doi:10.1074/jbc.m114.593210

Cited by 70 publications

(64 citation statements)

References 48 publications

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“…For example, palmitic acid negatively controls fibroblast function in the dermis . In addition, subcutaneous adipocyte‐derived palmitic acid enhances melanoma proliferation . Besides the regulation of fibroblasts and melanomas, our results indicate that palmitic acid induces REG3A expression in the HaCaT keratinocyte cell line and in normal human keratinocytes (Fig.…”

Section: Discussionmentioning

confidence: 58%

Obesity exacerbates imiquimod‐induced psoriasis‐like epidermal hyperplasia and interleukin‐17 and interleukin‐22 production in mice

Kanemaru

Matsuyuki

Nakamura

et al. 2015

Experimental Dermatology

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Psoriasis is a chronic inflammatory skin disorder that is accompanied by an imbalance between the proliferation and differentiation of keratinocytes. A number of studies have suggested an association between obesity and severe psoriasis; however, it remains to be clarified whether obesity exacerbates psoriasis. To address this unsolved question, we induced psoriasiform dermatitis in mouse models for obesity. We found that obesity exaggerated the severity of psoriasiform dermatitis induced by topical application of the Toll-like receptor (TLR) 7 agonist, imiquimod. Ear swelling and epidermal hyperplasia were more prominent in the obese mice than in the control mice. When compared to imiquimod-treated control mice, imiquimod-treated obese mice expressed higher levels of psoriasis mediators, interleukin-17A (IL-17A) and IL-22 in the skin. Food intake restriction partially abrogated enhanced ear swelling and cytokine overproduction in obese mice. Furthermore, the obesity environment and imiquimod treatment synergistically induced an IL-17A downstream molecule, regenerating islet-derived 3γ (Reg3γ), which is a critical molecule for psoriatic epidermal hyperplasia. Palmitic acid, one of the fatty acids released by subcutaneous adipocytes, increased the expression of REG3A (a human homologue of mouse Reg3γ) in both the HaCaT keratinocyte cell line and normal human keratinocytes. Taken together, these results strongly suggest that obesity exacerbates psoriasiform dermatitis in mice by upregulating IL-17A, IL-22 and Reg3γ.

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Section: Discussionmentioning

confidence: 58%

Obesity exacerbates imiquimod‐induced psoriasis‐like epidermal hyperplasia and interleukin‐17 and interleukin‐22 production in mice

Kanemaru

Matsuyuki

Nakamura

et al. 2015

Experimental Dermatology

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“…Indeed, CAF-derived EV transport metabolites, such as amino acids, lipids, and TCA cycle intermediates, to tumor cells, which serves as triggers for central carbon metabolism (Zhao et al, 2016). Even though we know FA are released by adipocytes in response to tumor secretions for transfer to melanoma cells (Kwan et al, 2014;Zhang et al, 2018), we reveal that naïve adipocytes, that have never encountered tumor secretions, can also convey lipids to cancer cells through EV. Previous studies had focused on the transfer of free FA from adipocytes to tumor cells and the role of FA transporters in their uptake.…”

Section: Discussionmentioning

confidence: 82%

Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells

et al. 2020

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Extracellular vesicles are emerging key actors in adipocyte communication. Notably, small extracellular vesicles shed by adipocytes stimulate fatty acid oxidation and migration in melanoma cells and these effects are enhanced in obesity. However, the vesicular actors and cellular processes involved remain largely unknown. Here, we elucidate the mechanisms linking adipocyte extracellular vesicles to metabolic remodeling and cell migration. We show that adipocyte vesicles stimulate melanoma fatty acid oxidation by providing both enzymes and substrates. In obesity, the heightened effect of extracellular vesicles depends on increased transport of fatty acids, not fatty acid oxidation-related enzymes. These fatty acids, stored within lipid droplets in cancer cells, drive fatty acid oxidation upon being released by lipophagy. This increase in mitochondrial activity redistributes mitochondria to membrane protrusions of migrating cells, which is necessary to increase cell migration in the presence of adipocyte vesicles. Our results provide key insights into the role of extracellular vesicles in the metabolic cooperation that takes place between adipocytes and tumors with particular relevance to obesity.

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“…There also are reports about saturated fatty acid C16:0 inhibiting proliferation through an autophagic mechanism in cancer cells . Kwan et al reported the opposite observation, that C16:0 promoted melanoma growth by activating Akt signaling in a phosphatase and tensin homolog–independent manner . On the other hand, unsaturated fatty acid C18:1 was reported to stimulate tumor growth through stabilization of β‐catenin .…”

Section: Discussionmentioning

confidence: 99%

Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism

et al. 2017

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Subcutaneous Adipocytes Promote Melanoma Cell Growth by Activating the Akt Signaling Pathway

Cited by 70 publications

References 48 publications

Obesity exacerbates imiquimod‐induced psoriasis‐like epidermal hyperplasia and interleukin‐17 and interleukin‐22 production in mice

Obesity exacerbates imiquimod‐induced psoriasis‐like epidermal hyperplasia and interleukin‐17 and interleukin‐22 production in mice

Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells

Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism

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