Transcriptomic study of the mechanism of anoikis resistance in head and neck squamous carcinoma

Guo, Cheng; Xu, Lingfeng; Li, Huimin; Wang, Wei; Guo, Jihua; Jia, Mengqi; Jia, Rong; Jia, Jun

doi:10.7717/peerj.6978

Cited by 8 publications

(9 citation statements)

References 83 publications

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“…EMT is the initial step of cancer invasion, dissemination, and metastasis, during which epithelial cells loss adhesion between tumor cells and the extracellular matrix (ECM) to acquire mesenchymal characteristics and invasive abilities [14,20]. Accumulating evidence has now indicated that EMT is one of the critical mechanisms that confers cancer cells resistance to anoikis [21][22][23][24][25], then creates a favorable opportunity for tumor proliferation, invasion, and metastasis [26]. It has been demonstrated that PI3K/AKT pathway is a major downstream pathway of miR-145-5p, which is involved in the regulation of invasion and metastasis in different tumor types, mainly in squamous cell carcinoma, bladder cancer and NSCLC [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

mir-145-5p is a suppressor of colorectal cancer at early stage, while promotes colorectal cancer metastasis at late stage through regulating AKT signaling evoked EMT-mediated anoikis

Cheng

Shen²,

Liu³

et al. 2022

BMC Cancer

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Background: miR-145-5P is generally considered as a tumor suppressor at early stage of colorectal cancer, but up-regulation occurs in the progressive and later stages which is associated with metastasis, indicating miR-145-5p may play dual role in colorectal cancer (CRC). To explore the detailed mechanism of miR-145-5p in carcinogenic is of importance. Methods: The expression pattern of miR-145-5p in CRC patients was downloaded from TCGA database, and the probable mechanism involved in the carcinogenic effect of miR-145-5p was predicted by bioinformatics analysis. Then, interference of miR-145-5p on SW480 and SW620 cells was conducted, and the influences on tumor cell viability, invasion ability, epithelial-mesenchymal transition (EMT), anoikis, and relative protein expression were examined respectively. Results: A total of 522 CRC patients’ data indicated that miR-145-5p expression was significantly higher in metastatic CRC than that in non-metastatic CRC, and higher expression of miR-145-5p was correlate with worse prognosis. Overexpression of miR-145-5P-5p enhanced the proliferation and invasion ability of SW620, but inhibited them in SW480. EMT was induced in SW620 after miR-145-5p overexpression and mesenchymal–epithelial transition (MET) was induced in SW480, resulted in the decreased apoptotic rate in SW620 and elevated apoptotic rate in SW480 respectively. Western blot results showed that AKT signaling pathway was involved in the miR-145-5p evoked EMT-mediated anoikis process in SW620 and SW480 cells. Conclusion: miR-145-5p is a tumor suppressor at early stage of CRC, and an oncogene at advanced stage of CRC. AKT signaling evoked EMT-mediated anoikis might be the pathway by which miR-145-5P regulates CRC cell invasion and metastasis.

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Section: Discussionmentioning

confidence: 99%

mir-145-5p is a suppressor of colorectal cancer at early stage, while promotes colorectal cancer metastasis at late stage through regulating AKT signaling evoked EMT-mediated anoikis

Cheng

Shen²,

Liu³

et al. 2022

BMC Cancer

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“…For instance, integrin-α2β1/-α5β1 interacted with epidermal growth factor receptor (EGFR) in the AR of colon cancer [29]. MiR-141/KLF12/Sp1/survivin signaling pathway enhanced AR in ovarian cancer, and a transcriptomic study addressed the importance of CDKN1A-regulated quiescence for cells to survive from anoikis in head and neck squamous carcinoma [30,31]. In accordance with the discoveries in previous studies, FASN, an enzyme implicated in the process of metabolism, has shown to be positively correlated with the development of various cancers, including GC [32][33][34].…”

Section: Discussionmentioning

confidence: 99%

FASN Knockdown Inhibited Anoikis Resistance of Gastric Cancer Cells via P-ERK1/2/Bcl-xL Pathway

Wang

et al. 2021

Gastroenterology Research and Practice

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Anoikis resistance (AR) is a crucial step in tumor metastasis. The overexpression of fatty acid synthase (FASN) is not only related to the AR of osteosarcoma cells, but also evidenced on gastric cancer (GC). This study investigated the role of FASN in the AR of GC cells. Plates coated with poly-HEMA were used for the culture of cells with AR. Small interfering RNA targeting FASN (siFASN) was transfected into MNK-45 and AGS cells. The number and apoptosis of cells were assessed by a hemacytometer and Annexin-V-FITC/PI assay, respectively. Aggregated cells and colony numbers were manually counted under a microscope. The migration and invasion rates were measured via wound healing and Transwell invasion assays, respectively. The levels of FASN, phosphorylated (p)-ERK1/2, ERK1/2 and Bcl-xL were detected through western blot or quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The results showed that the cell numbers of MNK-45 and AGS were increased while that of GES-1 cell was decreased during the culture in suspension. A higher apoptosis rate and a smaller number of aggregated cells were observed in GES-1 cells in comparison with MNK-45 and AGS cells. A larger colony number, greater migration and invasion rates, and higher mRNA and protein expressions of FASN were presented in the AR group compared with the control group. Cells transfected with siFASN possessed lower migration and invasion rates, reduced expressions of FASN mRNA and protein, p-ERK1/2 and Bcl-xL, and induced a significantly declined ratio of p-ERK1/2 to ERK1/2. These findings suggest that down-regulation of FASN suppresses the AR of GC cells, which may be related to the inhibition of p-ERK1/2/Bcl-xL pathway.

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Section: Introductionmentioning

confidence: 99%

“…[17] Anoikis resistance in HNSCC was found to be associated with the VEGFA-STAT3-KLF4-CDKN1A signaling pathway. [18] Anoikis resistance in HNSCC has also been linked to fibronectin. [19] The cause of anoikis resistance in HNSCC has been the subject of numerous research.…”

Section: Introductionmentioning

confidence: 99%

“…[19] The cause of anoikis resistance in HNSCC has been the subject of numerous research. [18] The process of epithelium cells changing into mesenchymal cells in response to certain normal and pathogenic stimuli is a frequent event in the development of HNSCC and is referred to as epithelial-mesenchymal transition. Many researchers now believe that the epithelial-mesenchymal transition process is a significant contributor to cancer cells developing anoikis resilience.…”

Section: Introductionmentioning

confidence: 99%

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Identification of a new anoikis-related gene signature for prognostic significance in head and neck squamous carcinomas

Wei,

Zhou,

Shen

et al. 2023

Medicine

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Anoikis, a mode of programmed cell death, is essential for normal development and homeostasis in the organism and plays an important role in the onset and progression of cancers. The authors of this research sought to establish a gene signature associated with anoikis to predict therapy outcomes and patient prognosis for individuals with head and neck squamous cell carcinoma (HNSCC). Transcriptome data of anoikis-related genes (ARGs) in individuals with HNSCC were retrieved from public databases to aid in the formulation of the gene signature. A novel ARG signature was then created using a combination of the Least Absolute Shrinkage and Selection Operator regression and Cox regression analysis. The relationship between ARGs and tumor immune microenvironment in HNSCC was explored using single-cell analysis. HNSCC individuals were classified into high-risk and low-risk groups as per the median value of risk score. The study also investigated the variations in the infiltration status of immune cells, tumor microenvironment, sensitivity to immunotherapy and chemotherapeutics, as well as functional enrichment between the low-risk and high-risk categories. A total of 18 ARGs were incorporated in the formulation of the signature. Our signature’s validity as a standalone predictive predictor was validated by multivariate Cox regression analysis and Kaplan–Meier survival analysis. Generally, the prognosis was worse for high-risk individuals. Subjects in the low-risk groups had a better prognosis and responded in a better way to combination immunotherapy, had higher immunological ratings and activity levels, and had more immune cell infiltration. In addition, gene set enrichment analysis findings showed that the low-risk subjects exhibited heightened activity in several immune-related pathways. However, the high-risk patients responded better to chemotherapy. The aim of this research was to develop a new ARG signature to predict the prognosis and sensitivity to immunotherapeutic and chemotherapeutic schemes for HNSCC patient. As a result, this could help spur the creation of new chemotherapeutics and immunotherapeutic approaches for patients with HNSCC.

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Transcriptomic study of the mechanism of anoikis resistance in head and neck squamous carcinoma

Cited by 8 publications

References 83 publications

mir-145-5p is a suppressor of colorectal cancer at early stage, while promotes colorectal cancer metastasis at late stage through regulating AKT signaling evoked EMT-mediated anoikis

mir-145-5p is a suppressor of colorectal cancer at early stage, while promotes colorectal cancer metastasis at late stage through regulating AKT signaling evoked EMT-mediated anoikis

FASN Knockdown Inhibited Anoikis Resistance of Gastric Cancer Cells via P-ERK1/2/Bcl-xL Pathway

Identification of a new anoikis-related gene signature for prognostic significance in head and neck squamous carcinomas

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