scholarly journals TRAP1 suppresses oral squamous cell carcinoma progression by reducing oxidative phosphorylation metabolism of Cancer-associated fibroblasts

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Li Xiao ◽  
Qiannan Hu ◽  
Yanshuang Peng ◽  
Kaiyue Zheng ◽  
Ting Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Glucose Metabolism ◽  
Oral Squamous Cell Carcinoma ◽  
Oxidative Phosphorylation ◽  
Cell Carcinoma ◽  
Quantitative Proteomics ◽  
Cancer Associated Fibroblasts ◽  
Label Free ◽  
Green Fluorescence ◽  
Atp Production

Abstract Background Glucose metabolism in cancer associated fibroblasts (CAFs) within the tumor microenvironment is a material and energy source for tumorigenesis and tumor development. However, the characteristics and important regulatory mechanisms of glucose metabolism in fibroblasts associated with oral squamous cell carcinoma (OSCC) are still unknown. Methods We successfully isolated, cultured, purified and identified CAFs and normal fibroblasts (NFs). Cell culture, immunohistochemistry (IHC) and CCK8, flow cytometry, Seahorse XF Analyzer, MitoTracker assay, western blotting (WB), transmission electron microscope, Quantitative real-time PCR (qPCR), immunofluorescence (IF), and Label-free quantitative proteomics assay, animal xenograft model studies and statistical analysis were applied in this study. Results We demonstrated that the proliferation activity of CAFs was significantly enhanced as compared to NFs, while the apoptosis rate was significantly decreased. CAFs in OSCC preferentially use oxidative phosphorylation (OXPHOS) rather than glycolysis. Moreover, CAFs showed stronger maximal respiration, a larger substantial mitochondrial spare respiratory capacity (SRC) and higher adenosine triphosphate (ATP) production capacity than NFs. The results of mitotracker green fluorescence staining showed that compared with NFs, CAFs exhibited stronger green fluorescence. The results of WB showed the expression level of Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) obviously increased in CAFs compared to NFs. These results confirmed that CAFs have greater mitochondrial activity and function than NFs. Furthermore, Label-free quantitative proteomics assays showed that both ATP synthase subunit O (ATP5O) and tumor necrosis factor receptor-associated protein 1 (TRAP1) are important differentially expressed proteins in the mitochondria of CAFs/NFs. Overexpression of TRAP1 in CAFs increased basal oxygen consumption rate (OCR), maximal respiration, ATP production and SRC. In vivo, overexpression TRAP1 expression in CAFs suppress tumor growth. Conclusion Taken together, the results indicated that TRAP1 is an important regulatory molecule of CAFs glucose metabolism and promotes OSCC progression by regulating the OXPHOS of CAFs.

scholarly journals CXCL1 induces senescence of cancer-associated fibroblasts via autocrine loops in oral squamous cell carcinoma

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0188847 ◽  
Author(s):  
Eun Kyoung Kim ◽  
Sook Moon ◽  
Do Kyeong Kim ◽  
Xianglan Zhang ◽  
Jin Kim
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cancer Associated Fibroblasts ◽  
Autocrine Loops

Immunohistochemical Characterization of Cancer-associated Fibroblasts in Oral Squamous Cell Carcinoma

2017 ◽  
pp. 1 ◽  
Author(s):  
Raísa C. Dourado ◽  
Lia P.A. Porto ◽  
Águida C.G.H. Leitão ◽  
Paloma S.G. Cerqueira ◽  
Jean N. dos Santos ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cancer Associated Fibroblasts

scholarly journals Differences in the Nemosis Response of Normal and Cancer-Associated Fibroblasts from Patients with Oral Squamous Cell Carcinoma

PLoS ONE ◽  
2009 ◽  
Vol 4 (9) ◽  
pp. e6879 ◽  
Author(s):  
Kati Räsänen ◽  
Ismo Virtanen ◽  
Pertteli Salmenperä ◽  
Reidar Grenman ◽  
Antti Vaheri
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cancer Associated Fibroblasts

scholarly journals MicroRNA-143 suppresses oral squamous cell carcinoma cell growth, invasion and glucose metabolism through targeting hexokinase 2

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Xianghui Sun ◽  
Lei Zhang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Migration ◽  
Glucose Metabolism ◽  
Oral Cancer ◽  
Tumor Suppressor ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Cell Lines ◽  
Oral Cancer Cells

miRNAs are non-coding RNAs that have functions to regulate gene expression and play essential roles in a variety of biological processes of cancers. In the present study, we report miR-143 acts as a tumor suppressor in human oral squamous cell carcinoma (OSCC). The expressions of miR-143 are down-regulated in both OSCC cell lines and patient samples compared with normal adjacent tissues. We found overexpression of miR-143 in oral cancer cell lines suppresses cell migration, cellular glucose metabolism and proliferation. Moreover, overexpression of miR-143 promoted apoptosis and significantly caused cell cycle arrest at G1 stage. The colony formation of oral cancer cells was also suppressed by miR-143. We identified hexokinase 2 (HK2) as a direct target of miR-143 in oral cancer cells. Our data show that miR-143 complementary pairs to the 3′-UTR of HK2 in oral cancer cells, leading to the inhibition of glycolysis in vitro and in vivo. Moreover, knockdown of HK2 by siRNA in oral cancer cells inhibited glucose metabolism, proliferation and migration. Recovery of glucose metabolism by overexpression of HK2 in miR-143 overexpressing cells restores the cell migration and proliferation, suggesting that the miR-143-mediated cancer suppression is through the direct inhibition of HK2. In summary, the present studies highlight miR-143 as a tumor suppressor in OSCC by the suppression of cell migration, glucose metabolism and proliferation through directly targeting HK2, rendering miR-143 a therapeutic strategy for the treatment of clinical OSCC patients.

scholarly journals Identification of lysine acetylome of oral squamous cell carcinoma by label-free quantitative proteomics

2021 ◽  
Author(s):  
Jingjing Dong ◽  
Jingquan He ◽  
Zeyu Zhang ◽  
Wei Zhang ◽  
Yixi Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Cellular Response ◽  
Enrichment Analysis ◽  
Lysine Acetylation ◽  
Label Free ◽  
Normal Tissues

Abstract Background Lysine acetylation (Kac) favors gene transcription and activates various genes involved in the regulation of oncogenesis, whereas the acetylation profiling of oral squamous cell carcinoma (OSCC) is unknown. We performed lysine acetylation analyses to achieve a comprehensive profile and revealed the specific pathogenesis in patients with OSCC. Methods Liquid chromatography − tandem mass spectrometry (LC-MS/MS) was utilized to investigate lysine acetylation features of tumor tissues and adjacent normal tissues from 9 patients with OCSS. Results Among the upregulated different acetylation proteins (DAPs), the biological process of GO analysis was closely related to cellular response to regulation of apoptotic process, and regulation of programmed cell death. KEGG enrichment analysis was associated with HIF-1 signaling pathway, ferroptosis, and JAK-STAT signaling pathway. In PPI network, seven differently Kac proteins (SRSF1, HNPNPM, PRPF8, DHX9, DHX15, RBMX, SNRPG) in MCODE1 and the top 30 hub gene involved in mRNA splicing process and spliceosome pathway. Six differently Kac modified proteins of RPS15A, RPL11, RPS11, RPS3, RPL24, RPL19 in MCODE1 was enriched in ribosome pathway, particular lower expression of RPS3, RPL24 and RPL19 were related to the overall survival of OSCC. Conclusion This study contributes a foundation for understanding the functions of Kac modification in OSCC and investigates lysine acetylation on proteins involved in ribosome pathway, particularly the ones that acted as hub genes and related to the OSCC survival, which may be a potential therapeutic direction of OSCC in the future.

scholarly journals The Axin2-snail axis promotes bone invasion by activating cancer-associated fibroblasts in oral squamous cell carcinoma

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yin-Zhe An ◽  
Eunae Cho ◽  
Junqi Ling ◽  
Xianglan Zhang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cancer Associated Fibroblasts ◽  
Bone Invasion ◽  
Biological Behaviour ◽  
Snail Expression

Abstract Background In bone-invasive oral squamous cell carcinoma (OSCC), cancer-associated fibroblasts (CAFs) infiltrate into bony tissue ahead of OSCC cells. In the present study, we aimed to investigate the role of the Axin2-Snail axis in the biological behaviour of CAFs and bone invasion in OSCC. Methods The clinicopathological significance of Axin2 and Snail expression was investigated by immunohistochemistry in an OSCC cohort containing 217 tissue samples from patients with long-term follow-up. The influence of the Axin2-Snail axis on the biological behaviour of OSCC cells and CAFs was further investigated both in vitro and in vivo. Results Axin2 expression was significantly associated with Snail expression, the desmoplasia status, and bone invasion in patients with OSCC. In multivariate analysis, lymph node metastasis, desmoplasia, Axin2 expression, and Snail expression were independent poor prognostic factors in our cohort. Consistent with these findings, OSCC cells demonstrated attenuated oncogenic activity as well as decreased expression of Snail and various cytokines after Axin2 knockdown in vitro. Among the related cytokines, C-C motif chemokine ligand 5 (CCL5) and interleukin 8 (IL8) demonstrated a strong influence on the biological behaviour of CAFs in vitro. Moreover, both the desmoplastic reaction and osteolytic lesions in the calvaria were predominantly decreased after Axin2 knockdown in OSCC cells in vivo using a BALB/c athymic nude mouse xenograft model. Conclusions Oncogenic activities of the Axin2-Snail axis are not limited to the cancer cells themselves but rather extend to CAFs via regulation of the cytokine-mediated cancer-stromal interaction, with further implications for bone invasion as well as a poor prognosis in OSCC.

Sign in / Sign up

Export Citation Format

Share Document