ADFP promotes cell proliferation in lung adenocarcinoma via Akt phosphorylation

Xia, Meng; Sun, Ruiying; Wang, Wei; Zhang, Na; Cao, Shiguang; Liu, Boxuan; Fang, Ping; Deng, Shanshan; Yang, Shuanying

doi:10.1111/jcmm.16136

Cited by 12 publications

(6 citation statements)

References 35 publications

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“…The possible interactions of these proteins were analyzed using bioinformatics, and several hub proteins were identified. Among these, we have already verified the expression and function of DHX9 ( Cao et al, 2017 ; Yan et al, 2019 ), ADFP ( Meng et al, 2021 ; Zhang et al, 2014 ), and GALNT2 ( Wang et al, 2021 ) in LUAD in vitro and in vivo models, patient databases and tissue samples. In the present study, we analyzed the role of SPC21 in LUAD progression and evaluated its value as a prognostic indicator and therapeutic target.…”

Section: Introductionmentioning

confidence: 84%

Signal peptidase 21 suppresses cell proliferation, migration, and invasion via the PTEN-PI3K/Akt signaling pathway in lung adenocarcinoma

Zhang

Cao

Sun

et al. 2022

PeerJ

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Background In a previous study, a total of 568 differentially expressed proteins including the signal peptidase SPC21 were identified from lung adenocarcinoma (LUAD) and paired normal lung tissues. In this study, the role of SPC21 in LUAD progression was investigated. Methods The relationships and protein-protein interaction network of proteins differentially expressed between paired LUAD samples and adjacent normal tissues samples were identified via the String and Pajek software, respectively. The expression levels of the hub protein SPC21 were analyzed in 84 LUAD-normal paired tissues via immunohistochemistry. The prognostic value of SPC21 mRNA was investigated in 478 LUAD patients from TCGA and GTEx datasets. siRNAs were used in A549 and NCI-H1299 cells to knockdown SPC21. The SPC21 biological function was evaluated using the CCK-8, EdU, plate colony formation, transwell, wound healing, and adhesion assays. Results Patients with lower SPC21 mRNA levels tended to have worse prognosis (overall survival) than those with higher mRNA levels. SPC21 expression was significantly downregulated in LUAD tumor tissues compared with that in paired normal tissues (P < 0.001). Functionally, SPC21 knockdown promoted cell growth, migration, and invasion. Further analyses showed that SPC21 inactivated Akt signaling, and the Akt inhibitor MK-2206 blocked the tumor-promoting effects of SPC21 knockdown. Conclusions SPC21 plays a tumor suppressor role in LUAD cells by targeting the PTEN-PI3K/Akt axis and might be used as a prognostic indicator and therapeutic target in LUAD patients.

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Section: Introductionmentioning

confidence: 84%

Signal peptidase 21 suppresses cell proliferation, migration, and invasion via the PTEN-PI3K/Akt signaling pathway in lung adenocarcinoma

Zhang

Cao

Sun

et al. 2022

PeerJ

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“…A pathological study found that PLIN2-positive lung adenocarcinoma was associated with a worse outcome reflected in overall and disease-free survival [89]. This was supported by basic research indicating that PLIN2 can promote lung adenocarcinoma cell proliferation by increasing the phosphorylation of Akt [90]. Kimberly et al reported that PLIN2 possesses potential in breast cancer subtype differentiation, as high-grade subtypes, namely, Her2-positive and TNBC, have lower expression of this protein [91].…”

Section: Plin2 and Plin3mentioning

confidence: 92%

Adding fuel to the fire: The lipid droplet and its associated proteins in cancer progression

Luo¹,

Wang²,

Lang³

et al. 2022

Int. J. Biol. Sci.

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A lipid droplet (LD) is an organelle that consists of a phospholipid monolayer and a neutral lipid core, with proteins embedded in or attached to its surface. Until recently, cancers had long been regarded as genetic disorders with the abnormal activation of oncogenes and inactivation of tumor suppressor genes before their quality of a metabolic disorder began to be recognized. The last decade has witnessed the recognition of several metabolic characteristics of cancer cells, among which one is the accumulation of lipid droplets; therefore, attention has been given to exploring the role of LDs in carcinomas. In addition, there has been a remarkable expansion in understanding the complexity of LD's function in cellular homeostasis, including but not limited to energy supply, endoplasmic reticulum (ER) stress and oxidative stress management, or lipotoxicity alleviation. Thus, lipid droplet-associated proteins, which to a great extent determine the dynamics of a lipid droplet, have attracted the interest of numerous cancer researchers and their potential as cancer diagnostic biomarkers and therapeutic targets has been affirmed by emerging evidence. In this review, we systematically summarize the critical role of LDs in cancer and then focus on four categories of lipid droplet-associated proteins having the most direct influence on LD biosynthesis (diacylglycerol acyltransferase 1 (DGAT1) and diacylglycerol acyltransferase 2 (DGAT2)), degradation (adipose triglyceride lipase (ATGL)), and two renowned protein families on the LD surface (perilipins and cell death-inducing DNA fragmentation factor alpha-like effectors (CIDEs)). In this way, we aim to highlight their important role in tumor progression and their potential in clinical applications.

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“…The association between PLIN2 and cancer is extensively documented. PLIN2 has been associated with tumorigenesis and is often considered as a poor prognosis indicator in cancers of the colon [90,91], breast [92,93], prostate [94,95], lung [96,97], bladder [95], kidney [82,[98][99][100][101][102][103][104][105], thyroid [106], gastric [107], and melanoma [108].…”

Section: Perilipinmentioning

confidence: 99%

Challenges in Pharmacological Intervention in Perilipins (PLINs) to Modulate Lipid Droplet Dynamics in Obesity and Cancer

Bombarda-Rocha,

Silva,

Badr-Eddine

et al. 2023

Cancers

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Perilipins (PLINs) are the most abundant proteins in lipid droplets (LD). These LD-associated proteins are responsible for upgrading LD from inert lipid storage structures to fully functional organelles, fundamentally integrated in the lipid metabolism. There are five distinct perilipins (PLIN1–5), each with specific expression patterns and metabolic activation, but all capable of regulating the activity of lipases on LD. This plurality creates a complex orchestrated mechanism that is directly related to the healthy balance between lipogenesis and lipolysis. Given the essential role of PLINs in the modulation of the lipid metabolism, these proteins can become interesting targets for the treatment of lipid-associated diseases. Since reprogrammed lipid metabolism is a recognized cancer hallmark, and obesity is a known risk factor for cancer and other comorbidities, the modulation of PLINs could either improve existing treatments or create new opportunities for the treatment of these diseases. Even though PLINs have not been, so far, directly considered for pharmacological interventions, there are many established drugs that can modulate PLINs activity. Therefore, the aim of this study is to assess the involvement of PLINs in diseases related to lipid metabolism dysregulation and whether PLINs can be viewed as potential therapeutic targets for cancer and obesity.

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ADFP promotes cell proliferation in lung adenocarcinoma via Akt phosphorylation

Cited by 12 publications

References 35 publications

Signal peptidase 21 suppresses cell proliferation, migration, and invasion via the PTEN-PI3K/Akt signaling pathway in lung adenocarcinoma

Signal peptidase 21 suppresses cell proliferation, migration, and invasion via the PTEN-PI3K/Akt signaling pathway in lung adenocarcinoma

Adding fuel to the fire: The lipid droplet and its associated proteins in cancer progression

Challenges in Pharmacological Intervention in Perilipins (PLINs) to Modulate Lipid Droplet Dynamics in Obesity and Cancer

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