A CD10‐OGP Membrane Peptolytic Signaling Axis in Fibroblasts Regulates Lipid Metabolism of Cancer Stem Cells via SCD1

Yu, Shubin; Lu, Yiwen; Su, An; Chen, Jianing; Jiang, Li; Zhou, Boxuan; Liu, Xinwei; Xia, Qi‐Dong; Li, Yihong; Li, Jiaqian; Huang, Min; Ye, Yingying; Zhao, Qiyi; Jiang, Sushi; Yan, Xiaoqing; Wang, Xiaojuan; Di, Can; Pan, Jiayao; Su, Shicheng

doi:10.1002/advs.202101848

Cited by 20 publications

(20 citation statements)

References 136 publications

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“…Subtype 2 exhibited a lower proportion of fibroblasts and a higher proportion of proliferating T cells and macrophages. Cancer-associated fibroblasts (CAFs) are not only important components of the BC microenvironment and are essential in tumor growth and development, but also have complex phenotypes and functional heterogeneity [ 56 , 57 , 58 , 59 ]. T cell proliferation is closely related to immune response, treatment resistance, and prognosis of BC [ 60 , 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

Unsupervised Analysis Based on DCE-MRI Radiomics Features Revealed Three Novel Breast Cancer Subtypes with Distinct Clinical Outcomes and Biological Characteristics

Ming

Zhu

et al. 2022

Cancers

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Background: This study aimed to reveal the heterogeneity of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of breast cancer (BC) and identify its prognosis values and molecular characteristics. Methods: Two radiogenomics cohorts (n = 246) were collected and tumor regions were segmented semi-automatically. A total of 174 radiomics features were extracted, and the imaging subtypes were identified and validated by unsupervised analysis. A gene-profile-based classifier was developed to predict the imaging subtypes. The prognostic differences and the biological and microenvironment characteristics of subtypes were uncovered by bioinformatics analysis. Results: Three imaging subtypes were identified and showed high reproducibility. The subtypes differed remarkably in tumor sizes and enhancement patterns, exhibiting significantly different disease-free survival (DFS) or overall survival (OS) in the discovery cohort (p = 0.024) and prognosis datasets (p ranged from <0.0001 to 0.0071). Large sizes and rapidly enhanced tumors usually had the worst outcomes. Associations were found between imaging subtypes and the established subtypes or clinical stages (p ranged from <0.001 to 0.011). Imaging subtypes were distinct in cell cycle and extracellular matrix (ECM)-receptor interaction pathways (false discovery rate, FDR < 0.25) and different in cellular fractions, such as cancer-associated fibroblasts (p < 0.05). Conclusions: The imaging subtypes had different clinical outcomes and biological characteristics, which may serve as potential biomarkers.

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Section: Discussionmentioning

confidence: 99%

Unsupervised Analysis Based on DCE-MRI Radiomics Features Revealed Three Novel Breast Cancer Subtypes with Distinct Clinical Outcomes and Biological Characteristics

Ming

Zhu

et al. 2022

Cancers

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“…SCD1 is a central lipogenic enzyme that catalyzes the synthesis of monounsaturated fatty acids (MUFA) during lipogenesis in human [41], and it was significantly downregulated after the KO of HIF-1α. SCD1 is known to play an essential role in the progression of cancers [42]. Gao et al found that SCD1 promoted the stemness of ovarian cancer stem cells through the Hippo/YAP pathway [43].…”

Section: Discussionmentioning

confidence: 99%

Stearoyl-CoA Desaturase-1 dependent lipid droplets accumulation in cancer-associated fibroblasts facilitates the progression of lung cancer

Zhang¹,

Gu²,

Wan³

et al. 2022

Int. J. Biol. Sci.

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Rationale: Cancer-associated fibroblasts (CAFs) are the main components in the tumor microenvironment (TME) and facilitate lung cancer progression. Studies have reported that metabolic reprogramming can regulate the function of CAFs, especially abnormal lipid metabolism. Lipid droplets (LDs) are ubiquitous organelles that store neutral lipids and have a crucial role in lipid metabolism. However, little is known about the synthesis and functions of LDs in lung CAFs. Methods: TetO-EGFR L858R ; CCSP-rtTA transgenic mouse model was used to establish a spontaneous pulmonary tumor model and investigate the accumulation of LDs in CAFs. The effect of LDs accumulation on the phenotype change of fibroblasts was estimated in vitro using mouse fibroblast cell lines. RNA sequencing, Western blotting, RT-PCR, and DNA-pull down were performed to determine the mechanism of LDs synthesis in fibroblasts. Results: We found that LDs were enriched in lung CAFs and induced the pro-tumoral phenotype of CAFs with increased expression of α-smooth muscle actin (α-SMA) and Collagen alpha-2 (I) chain (COL1A2). As the main regulator, hypoxia-inducible factor-1α (HIF-1α) was highly expressed in activated fibroblasts and increased the content of LDs. RNA-sequencing results showed that Stearoyl-CoA Desaturase1 (SCD1) was a downstream gene of HIF-1α, which upregulated the number of LDs in fibroblasts. Importantly, SCD1 inhibition reduced the growth of lung tumors, which was correlated with LDs decrease in CAFs. Analysis of human lung adenocarcinoma tissue chip revealed that CAFs with a high level of SCD1 were positively correlated with the expression of HIF-1α and poor survival in lung cancer patients. Conclusions:The HIF-1α/SCD1 axis regulates the accumulation of LDs in CAFs, which might represent a novel target for lung cancer therapy.

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“…Dysregulated lipid metabolism is crucial for maintaining CSC stemness properties and fulfilling their energy demands [30,31]. CSC fate decision is reliant on the activity of enzymes involved in lipid metabolism, such as SCD1 [32]. SCD1 is a key enzyme to convert saturated fatty acids into monounsaturated fatty acids (MUFAs), which is involved in the tumorigenesis of multiple cancers, including gastric cancer [33].…”

Section: Discussionmentioning

confidence: 99%

AKAP8L enhances the stemness and chemoresistance of gastric cancer cells by stabilizing SCD1 mRNA

et al. 2022

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Gastric cancer (GC) remains the third leading cause of cancer-related deaths. Chemoresistance is the major determinant of GC treatment failure. To explore the molecular mechanisms of GC chemoresistance, mass spectrometry was performed to detect the genes altered in expression between chemoresistant and chemosensitive GC. PRKA kinase anchor protein 8L (AKAP-8L) was identified as one of the top upregulated genes in chemoresistant GC tissues. Moreover, the higher AKAP-8L expression was associated with the lower survival rate in GC patients. Overexpression of AKAP-8L enhanced the GC cell stemness and chemoresistance of oxaliplatin in vivo and in vitro. AKAP-8L deficiency obtained the opposite results. Mechanistically, AKAP-8L interacted with Stearoyl-CoA desaturase 1 (SCD1) mRNA and IGF2BP1 protein, and regulated SCD1 mRNA stability via IGF2BP1-dependent manner. SCD1 played a critical role in mediating the function of AKAP-8L in GC cell stemness and chemoresistance. Clinically, AKAP-8L and SCD1 protein levels was positively associated with human GC chemoresistance. Taken together, our results demonstrated that AKAP-8L facilitates GC chemoresistance via regulating SCD1-mediated stemness of GC cells. AKAP8L may represent a novel therapeutic target to overcome GC chemoresistance.

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A CD10‐OGP Membrane Peptolytic Signaling Axis in Fibroblasts Regulates Lipid Metabolism of Cancer Stem Cells via SCD1

Cited by 20 publications

References 136 publications

Unsupervised Analysis Based on DCE-MRI Radiomics Features Revealed Three Novel Breast Cancer Subtypes with Distinct Clinical Outcomes and Biological Characteristics

Unsupervised Analysis Based on DCE-MRI Radiomics Features Revealed Three Novel Breast Cancer Subtypes with Distinct Clinical Outcomes and Biological Characteristics

Stearoyl-CoA Desaturase-1 dependent lipid droplets accumulation in cancer-associated fibroblasts facilitates the progression of lung cancer

AKAP8L enhances the stemness and chemoresistance of gastric cancer cells by stabilizing SCD1 mRNA

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