Low expression of IGFBP4 and TAGLN accelerate the poor overall survival of osteosarcoma

Xi, Yue; Liu, Jianlin; Shen, Guoyu

doi:10.1038/s41598-022-13163-8

Cited by 3 publications

(3 citation statements)

References 32 publications

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“…TNC, LUM, COL12A1, COL6A3, and BGN are among the DEPs that differentiate the chondroblastic group from other subtypes of osteosarcoma. TNC, or tenascin, was highly expressed in osteosarcoma tissues compared to normal [39]. LUM, or lumican, may be positively correlated with the differentiation and negatively correlated with the progression of osteosarcoma [40].…”

Section: Discussionmentioning

confidence: 94%

Comparative Shotgun Proteomics Reveals the Characteristic Protein Signature of Osteosarcoma Subtypes

Alaa,

Al-Shehaby,

Anwar

et al. 2023

Cells

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Osteosarcoma is a primary malignant bone tumor affecting adolescents and young adults. This study aimed to identify proteomic signatures that distinguish between different osteosarcoma subtypes, providing insights into their molecular heterogeneity and potential implications for personalized treatment approaches. Using advanced proteomic techniques, we analyzed FFPE tumor samples from a cohort of pediatric osteosarcoma patients representing four various subtypes. Differential expression analysis revealed a significant proteomic signature that discriminated between these subtypes, highlighting distinct molecular profiles associated with different tumor characteristics. In contrast, clinical determinants did not correlate with the proteome signature of pediatric osteosarcoma. The identified proteomics signature encompassed a diverse array of proteins involved in focal adhesion, ECM-receptor interaction, PI3K-Akt signaling pathways, and proteoglycans in cancer, among the top enriched pathways. These findings underscore the importance of considering the molecular heterogeneity of osteosarcoma during diagnosis or even when developing personalized treatment strategies. By identifying subtype-specific proteomics signatures, clinicians may be able to tailor therapy regimens to individual patients, optimizing treatment efficacy and minimizing adverse effects.

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Section: Discussionmentioning

confidence: 94%

Comparative Shotgun Proteomics Reveals the Characteristic Protein Signature of Osteosarcoma Subtypes

Alaa,

Al-Shehaby,

Anwar

et al. 2023

Cells

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“…Transgelin (TAGLN; also known as SM22), an actinbinding protein, is mainly associated with cytoskeleton remodeling (27). In several types of tumor, such as prostate cancer, osteosarcoma and breast cancer, the expression level of TAGLN has been shown to be reduced, or even entirely deleted (28)(29)(30). An association between the expression of TAGLN and the occurrence, development and invasion of tumors has also been reported in several studies (31)(32)(33).…”

Section: Transgelin Promotes Ferroptosis To Inhibit the Malignant Pro...mentioning

confidence: 88%

Transgelin promotes ferroptosis to inhibit the malignant progression of esophageal squamous cell carcinoma

Chen,

Zhang,

Wan

et al. 2023

Int J Oncol

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The aim of the present study was to examine the function of transgelin (TAGLN) and its underlying mechanism in the ferroptosis of esophageal squamous cell carcinoma (ESCC) cells. To meet this aim, the association between TAGLN expression and the prognosis of patients with ESCC was determined using tissue samples and clinical data. Gene Expression Omnibus databank and Gene Set Enrichment Analysis data were used to examine which genes were co-expressed with TAGLN, as well as the influence of TAGLN on ESCC. Subsequently, Transwell chamber, wound healing, Cell Counting Kit-8 viability and colony formation assays were performed to observe the effects of TAGLN on the migration, invasion, viability and proliferation of Eca-109 and KYSE-150 cells. The interaction between TAGLN and p53 in the regulation of ferroptosis was detected using reverse transcription-quantitative PCR, co-immunoprecipitation and fluorescence co-localization assays, and a xenograft tumor model was established to examine the effect of TAGLN on tumor growth. The level of TAGLN expression in patients with ESCC was found to be low, compared with normal esophageal tissue, and a positive association was identified between the prognosis of ESCC and TAGLN expression. The expression of the ferroptosis marker protein, glutathione peroxidase 4, was found to be high, whereas that of acyl-CoA synthetase long-chain family member 4 was lower in patients with ESCC compared with expression levels in healthy patients. The overexpression of TAGLN resulted in a significant decrease in the invasive and proliferative capabilities of Eca-109 and KYSE-150 cells in vitro compared with the control group; in vivo, TAGLN overexpression was found to significantly decrease tumor size, volume and weight after one month of growth. In addition, the proliferation, migration and invasion of Eca-109 cells in vivo was stimulated by the knockdown of TAGLN. The results of the transcriptome analysis further demonstrated that TAGLN was able to induce ferroptosis-associated cell functions and pathways. Finally, TAGLN overexpression was found to promote ferroptosis in ESCC through its interaction with p53. Taken together, the findings of the present study suggested that the malignant development of ESCC may be inhibited by TAGLN through the manifestation of ferroptosis.

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“…Cytoscape (cytoHubba) was used to identify and select hub genes with the Degree method [24]. Because of the different numbers of DEGs depending on the duration of hypoxia, we selected the top 10 and top 20 genes for acute and chronic hypoxia, respectively, and displayed them in their corresponding network (Fig.…”

Section: Identification Of Hypoxia-related Hub Genes and Their Clinic...mentioning

confidence: 99%

Differential response of luminal and basal breast cancer cells to acute and chronic hypoxia

Liu

Noord

et al. 2023

Breast Cancer Res Treat

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Hypoxia is linked to disease progression and poor prognosis in several cancers, including breast cancer. Cancer cells can encounter acute, chronic, and/or intermittent periods of oxygen deprivation and it is poorly understood how the different breast cancer subtypes respond to such hypoxia regimes. Here, we assessed the response of representative cell lines for the luminal and basal A subtype to acute (24 h) and chronic hypoxia (5 days). High throughput targeted transcriptomics analysis showed that HIF-related pathways are significantly activated in both subtypes. Indeed, HIF1⍺ nuclear accumulation and activation of the HIF1⍺ target gene CA9 were comparable. Based on the number of differentially expressed genes: (i) 5 days of exposure to hypoxia induced a more profound transcriptional reprogramming than 24 h, and (ii) basal A cells were less affected by acute and chronic hypoxia as compared to luminal cells. Hypoxia-regulated gene networks were identified of which hub genes were associated with worse survival in breast cancer patients. Notably, while chronic hypoxia altered the regulation of the cell cycle in both cell lines, it induced two distinct adaptation programs in these subtypes. Mainly genes controlling central carbon metabolism were affected in the luminal cells whereas genes controlling the cytoskeleton were affected in the basal A cells. In agreement, in response to chronic hypoxia, lactate secretion was more prominently increased in the luminal cell lines which were associated with the upregulation of the GAPDH glycolytic enzyme. This was not observed in the basal A cell lines. In contrast, basal A cells displayed enhanced cell migration associated with more F-actin stress fibers whereas luminal cells did not. Altogether, these data show distinct responses to acute and chronic hypoxia that differ considerably between luminal and basal A cells. This differential adaptation is expected to play a role in the progression of these different breast cancer subtypes.

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Low expression of IGFBP4 and TAGLN accelerate the poor overall survival of osteosarcoma

Cited by 3 publications

References 32 publications

Comparative Shotgun Proteomics Reveals the Characteristic Protein Signature of Osteosarcoma Subtypes

Comparative Shotgun Proteomics Reveals the Characteristic Protein Signature of Osteosarcoma Subtypes

Transgelin promotes ferroptosis to inhibit the malignant progression of esophageal squamous cell carcinoma

Differential response of luminal and basal breast cancer cells to acute and chronic hypoxia

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