Silencing PLOD2 attenuates cancer stem cell-like characteristics and cisplatin-resistant through Integrin β1 in laryngeal cancer

Song, Meiyan; Liu, Xing; Li, Tao; Zhang, Yueqin; Zhao, Xiao‐Fan; Sun, Wei; Li, Zhen

doi:10.1016/j.tranon.2022.101460

Cited by 10 publications

(4 citation statements)

References 34 publications

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“…In this study, we found that lipid homeostasis correlated significantly with multidrug resistance in GC. In particular, PLOD2 is reported to stimulate the cancer stem cell phenotype and cisplatin resistance in cancer 38 . TGFB2 is a common cytokine involved in intercellular communication and FOLFOX resistance 39 , and we found that it was strongly associated with chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

Identification of a lipid homeostasis-related gene signature for predicting prognosis, immunity, and chemotherapeutic effect in patients with gastric cancer

Li,

Xiong,

Han

et al. 2024

Sci Rep

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Gastric cancer (GC) is one of the most common and deadliest cancers worldwide. Lipid homeostasis is essential for tumour development because lipid metabolism is one of the most important metabolic reprogramming pathways within tumours. Elucidating the mechanism of lipid homeostasis in GC might significantly improve treatment strategies and patient prognosis. GSE62254 was applied to construct a lipid homeostasis-related gene signature score (HGSscore) by multiple bioinformatic algorithms including weighted gene coexpression network analysis (WGCNA) and LASSO-Cox regression. A nomogram based on HGSscore and relevant clinical characteristics was constructed to predict the survival of patients with GC. TIMER and xCell were used to evaluate immune and stromal cell infiltration in the tumour microenvironment. Correlations between lipid homeostasis-related genes and chemotherapeutic efficacy were analysed in GSCAlite. RT‒qPCR and cell viability assays were applied to verify the findings in this study. HGSscore was constructed based on eighteen lipid homeostasis-related genes that were selected by WGCNA and LASSO-Cox regression. HGSscore was strongly associated with advanced TNM stage and showed satisfactory value in predicting GC prognosis in three independent cohorts. Furthermore, we found that HGSscore was associated with the tumour mutation burden (TMB) and immune/stromal cell infiltration, which are related to GC prognosis, indicating that lipid homeostasis impacts the formation of the tumour microenvironment (TME). With respect to the GSCAlite platform, PLOD2 and TGFB2 were shown to be positively related to chemotherapeutic resistance, while SLC10A7 was a favourable factor for chemotherapy efficacy. Cell viability assays showed that disrupted lipid homeostasis could attenuate GC cell viability. Moreover, RT‒qPCR revealed that lipid homeostasis could influence expression of specific genes. We identified a lipid homeostasis-related gene signature that correlated with survival, clinical characteristics, the TME, and chemotherapeutic efficacy in GC patients. This research provides a new perspective for improving prognosis and guiding individualized chemotherapy for patients with GC.

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Section: Discussionmentioning

confidence: 99%

Identification of a lipid homeostasis-related gene signature for predicting prognosis, immunity, and chemotherapeutic effect in patients with gastric cancer

Li,

Xiong,

Han

et al. 2024

Sci Rep

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“…PLOD2, which provides attachment sites for carbohydrates in collagen, was also initially reviewed as a potential prognostic factor [42]. Recent clinicopathological studies have highlighted an inversed relationship between its high expression and overall survival in patients with esophageal squamous cell carcinoma [43], glioblastoma [44], laryngeal cancer [45], or osteosarcoma [46]. Moreover, an inverse relationship was also observed with immune cell infiltration [46].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Deeply Versus Mildly Invasive Mesothelioma Proteomes Identifies Potential Links Between Mitochondrial Acadvl Expression and Biomarkers of Aggressiveness

Pouliquen¹,

Kopecka²,

Blandin³

et al. 2023

Preprint

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Recent reports suggest that dysregulation of lipid metabolism is a key feature of the most invasive cancers. To identify potential biomarkers of tumor aggressiveness, we compared the proteomes of two experimental models of malignant mesothelioma in rats exhibiting different invasive properties. Quantitative changes between the most invasive, M5-T1, versus the least invasive, F4-T2, first led to a list of 424 proteins. A second step, cross-comparing this list with 433 proteins distinguishing invasive vs non-invasive tumors, led to identifying 88 proteins that specifically increased and 157 that decreased, respectively, characterizing the most aggressive M5-T1 tumor. Among the 15 mitochondrial proteins found in these lists, the very long-chain specific acyl-CoA dehydrogenase, encoded by the Acadvl gene and involved in fatty acid beta oxidation, appeared to play an important role in the metabolic reprogramming of the tumor microenvironment. Immunohistochemical staining of tumor sections confirmed increased expression of Acadvl in the M5-T1 tumor. Finally, the dramatic increase and decrease, observed in 25 and 17 proteins, respectively, suggested the existence of a strong link between mitochondrial events and modifications of the extracellular matrix, immune cell components or other subcellular compartments. These findings highlight some important aspects of the tumor microenvironment changes linked to aggressiveness.

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“…PLOD2 modulated tumorigenesis and LC cell stemness in cisplatin-resistant nude mice through Integrin β1. In addition, PLOD2 silencing reduced tumor progression and stemness in CDDP-resistant LC cells by suppressing P-gp and MRP1 through Integrin β1 [ 165 ].…”

Section: Mapk and Wnt/β-catenin Signaling Pathwaysmentioning

confidence: 99%

Integrins as the pivotal regulators of cisplatin response in tumor cells

Nasimi Shad,

Moghbeli

2024

Cell Commun Signal

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Cisplatin (CDDP) is a widely used first-line chemotherapeutic drug in various cancers. However, CDDP resistance is frequently observed in cancer patients. Therefore, it is required to evaluate the molecular mechanisms associated with CDDP resistance to improve prognosis among cancer patients. Integrins are critical factors involved in tumor metastasis that regulate cell-matrix and cell-cell interactions. They modulate several cellular mechanisms including proliferation, invasion, angiogenesis, polarity, and chemo resistance. Modification of integrin expression levels can be associated with both tumor progression and inhibition. Integrins are also involved in drug resistance of various solid tumors through modulation of the tumor cell interactions with interstitial matrix and extracellular matrix (ECM). Therefore, in the present review we discussed the role of integrin protein family in regulation of CDDP response in tumor cells. It has been reported that integrins mainly promoted the CDDP resistance through interaction with PI3K/AKT, MAPK, and WNT signaling pathways. They also regulated the CDDP mediated apoptosis in tumor cells. This review paves the way to suggest the integrins as the reliable therapeutic targets to improve CDDP response in tumor cells.

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Silencing PLOD2 attenuates cancer stem cell-like characteristics and cisplatin-resistant through Integrin β1 in laryngeal cancer

Cited by 10 publications

References 34 publications

Identification of a lipid homeostasis-related gene signature for predicting prognosis, immunity, and chemotherapeutic effect in patients with gastric cancer

Identification of a lipid homeostasis-related gene signature for predicting prognosis, immunity, and chemotherapeutic effect in patients with gastric cancer

Comparison of Deeply Versus Mildly Invasive Mesothelioma Proteomes Identifies Potential Links Between Mitochondrial Acadvl Expression and Biomarkers of Aggressiveness

Integrins as the pivotal regulators of cisplatin response in tumor cells

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