Adipophilin expression in cutaneous malignant melanoma is associated with high proliferation and poor clinical prognosis

Fujimoto, Masakazu; Matsuzaki, Ibu; Nishitsuji, Kazuchika; Yamamoto, Yuki; Murakami, Daisuke; Yoshikawa, Takanori; Fukui, A.; Mori, Y.; Nishino, Masaru; Takahashi, Yuichi; Iwahashi, Yoshifumi; Warigaya, Kenji; Kojima, Fumiyoshi; Jinnin, Masatoshi; Murata, Shin‐ichi

doi:10.1038/s41374-019-0358-y

Cited by 27 publications

(36 citation statements)

References 47 publications

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“…White adipocytes are fat cells known for their large unilocular lipid droplet ( Fujimoto and Parton, 2011 ; Heid et al, 2014 ), so we expected expression of the PLIN2-tdTOMATO fusion protein on the surface of the adipocyte lipid droplet ( Figure 1A ). Since the adipocyte lipid droplet occupies the majority of space in the cell ( Fujimoto et al, 2020 ), existing methods to visualize zebrafish adipocytes rely on lipophilic dyes and lipid analogs, which incorporate into the lipid droplet ( Zhang et al, 2018 ). Thus, in addition to labeling individual lipid droplets, we reasoned that the PLIN2-tdTOMATO fusion protein can also function as a reporter for adipocytes since these cells would have the largest and unilocular lipid droplets.…”

Section: Resultsmentioning

confidence: 99%

“…Upon uptake of adipocyte-derived lipids, cancer cells can store excess lipids in lipid droplets ( Lengyel et al, 2018 ). Accumulation of lipid droplets in melanoma cells has been associated with increased metastatic potential and worse clinical outcomes ( Fujimoto et al, 2020 ; Zhang et al, 2018 ). The mechanisms regulating subsequent lipolysis from the lipid droplets in cancer cells are not well understood, but we reasoned that some of the same mechanisms (i.e., ATGL, nitric oxide) used in adipocytes might also be used in cancer cells.…”

Section: Resultsmentioning

confidence: 99%

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An in vivo reporter for tracking lipid droplet dynamics in transparent zebrafish

Lumaquin

Johns

Montal

et al. 2021

eLife

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Lipid droplets are lipid storage organelles found in nearly all cell types from adipocytes to cancer cells. Although increasingly implicated in disease, current methods to study lipid droplets in vertebrate models rely on static imaging or the use of fluorescent dyes, limiting investigation of their rapid in vivo dynamics. To address this, we created a lipid droplet transgenic reporter in whole animals and cell culture by fusing tdTOMATO to Perilipin-2 (PLIN2), a lipid droplet structural protein. Expression of this transgene in transparent casper zebrafish enabled in vivo imaging of adipose depots responsive to nutrient deprivation and high-fat diet. Simultaneously, we performed a large-scale in vitro chemical screen of 1280 compounds and identified several novel regulators of lipolysis in adipocytes. Using our Tg(-3.5ubb:plin2-tdTomato) zebrafish line, we validated several of these novel regulators and revealed an unexpected role for nitric oxide in modulating adipocyte lipid droplets. Similarly, we expressed the PLIN2-tdTOMATO transgene in melanoma cells and found that the nitric oxide pathway also regulated lipid droplets in cancer. This model offers a tractable imaging platform to study lipid droplets across cell types and disease contexts using chemical, dietary, or genetic perturbations.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

An in vivo reporter for tracking lipid droplet dynamics in transparent zebrafish

Lumaquin

Johns

Montal

et al. 2021

eLife

View full text Add to dashboard Cite

show abstract

“…Fujimoto & Parton, 2011; Heid et al, 2014) so we expected expression of the PLIN2-tdTOMATO fusion protein on the surface of the adipocyte lipid droplet (Figure 1A). Since the adipocyte lipid droplet occupies the majority of space in the cell (M. Fujimoto et al, 2020), existing methods to visualize zebrafish adipocytes rely on lipophilic dyes and lipid analogs which incorporate in the lipid droplet (Zhang et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

“…White adipocytes are fat cells known for their large unilocular lipid droplet (T. Fujimoto & Parton, 2011;Heid et al, 2014) so we expected expression of the PLIN2-tdTOMATO fusion protein on the surface of the adipocyte lipid droplet ( Figure 1A). Since the adipocyte lipid droplet occupies the majority of space in the cell (M. Fujimoto et al, 2020), existing methods to visualize zebrafish adipocytes rely on lipophilic dyes and lipid analogs which incorporate in the lipid droplet (Zhang et al, 2018). Thus in addition to labeling individual lipid droplets, we reasoned that the PLIN2-tdTOMATO fusion protein can also function as a reporter for adipocytes since these cells would have the largest and unilocular lipid droplets.…”

Section: An In Vivo Lipid Droplet Reporter Using a Plin2-tdtomato Fusmentioning

confidence: 99%

“…Upon uptake of adipocyte-derived lipids, cancer cells can store excess lipids in lipid droplets (Lengyel et al, 2018). Accumulation of lipid droplets in melanoma cells has been associated with increased metastatic potential and worse clinical outcomes (M. Fujimoto et al, 2020;Zhang et al, 2018). The mechanisms regulating subsequent lipolysis from the lipid droplets in cancer cells are not well understood, but we reasoned that some of the same mechanisms (i.e.…”

Section: Lipolysis Modulators Also Inhibit Lipid Droplet Loss In Melamentioning

confidence: 99%

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Anin vivoreporter for tracking lipid droplet dynamics in transparent zebrafish

Lumaquin

Johns

Weiss

et al. 2020

Preprint

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Lipid droplets are lipid storage organelles found in nearly all cell types from adipocytes to cancer cells. Although increasingly implicated in disease, current methods to study lipid droplets require fixation or static imaging which limits investigation of their rapid in vivo dynamics. To address this, we created a lipid droplet transgenic reporter in whole animals and cell culture by fusing tdTOMATO to Perilipin-2 (PLIN2), a lipid droplet structural protein. Expression of this transgene in transparent casper zebrafish enabled in vivo imaging of adipose depots responsive to nutrient deprivation and high-fat diet. Using this system, we tested novel regulators of lipolysis, revealing an unexpected role for nitric oxide in modulating adipocyte lipid droplets. Similarly, we expressed the PLIN2-tdTOMATO transgene in melanoma cells and found that the nitric oxide pathway also regulated lipid droplets in cancer. This model offers a tractable imaging platform to study lipid droplets across cell types and disease contexts.

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Lipid droplets provide metabolic flexibility for cancer progression

Safi,

Menéndez,

Pol

2024

FEBS Letters

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A hallmark of cancer cells is their remarkable ability to efficiently adapt to favorable and hostile environments. Due to a unique metabolic flexibility, tumor cells can grow even in the absence of extracellular nutrients or in stressful scenarios. To achieve this, cancer cells need large amounts of lipids to build membranes, synthesize lipid‐derived molecules, and generate metabolic energy in the absence of other nutrients. Tumor cells potentiate strategies to obtain lipids from other cells, metabolic pathways to synthesize new lipids, and mechanisms for efficient storage, mobilization, and utilization of these lipids. Lipid droplets (LDs) are the organelles that collect and supply lipids in eukaryotes and it is increasingly recognized that the accumulation of LDs is a new hallmark of cancer cells. Furthermore, an active role of LD proteins in processes underlying tumorigenesis has been proposed. Here, by focusing on three major classes of LD‐resident proteins (perilipins, lipases, and acyl‐CoA synthetases), we provide an overview of the contribution of LDs to cancer progression and discuss the role of LD proteins during the proliferation, invasion, metastasis, apoptosis, and stemness of cancer cells.

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Adipophilin expression in cutaneous malignant melanoma is associated with high proliferation and poor clinical prognosis

Cited by 27 publications

References 47 publications

An in vivo reporter for tracking lipid droplet dynamics in transparent zebrafish

An in vivo reporter for tracking lipid droplet dynamics in transparent zebrafish

Anin vivoreporter for tracking lipid droplet dynamics in transparent zebrafish

Lipid droplets provide metabolic flexibility for cancer progression

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