Transcriptional Regulation of GDF15 by EGR1 Promotes Head and Neck Cancer Progression through a Positive Feedback Loop

Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor-β (TGF-β) superfamily, has been reported to be overexpressed in different kinds of cancer types. However, the function and mechanism of GDF15 in head and neck cancer (HNC) remains unclear. The Cancer Genome Atlas (TCGA) data show that the expression of GDF15 is significantly associated with tumor AJCC stage, lymph vascular invasion and tumor grade in HNC. In this study, we confirmed that knockdown of GDF15 attenuated: cell proliferation, migration and invasion via regulation of EMT through a canonical pathway; SMAD2/3 and noncanonical pathways; PI3K/AKT and MEK/ERK in HNC cell lines. Furthermore, we found that early growth response 1 (EGR1) was a transcription factor of GDF15. Interestingly, we also demonstrated that GDF15 could regulate the expression of EGR1, which meant a positive feedback loop occurred between these two factors. Moreover, combined inhibition of both GDF15 and EGR1 in a HNC mouse xenograft model showed significantly decreased tumor volume compared to inhibition of EGR1 or GDF15 alone. Our study showed that the GDF15–EGR1 signaling axis may be a good target in HNC patients.

Download Full-text

A positive feedback loop between HER2 and ADAM12 in human head and neck cancer cells increases migration and invasion

Oncogene ◽

10.1038/onc.2011.460 ◽

2011 ◽

Vol 31 (23) ◽

pp. 2888-2898 ◽

Cited By ~ 27

Author(s):

V H Rao ◽

A Kandel ◽

D Lynch ◽

Z Pena ◽

N Marwaha ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Cancer Cells ◽

Neck Cancer ◽

Positive Feedback ◽

Feedback Loop ◽

Human Head ◽

Migration And Invasion ◽

Positive Feedback Loop

Download Full-text

Profilin 2 Promotes Proliferation and Metastasis of Head and Neck Cancer Cells by Regulating PI3K/AKT/β-Catenin Signaling Pathway

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504019x15579146061957 ◽

2019 ◽

Vol 27 (9) ◽

pp. 1079-1088 ◽

Cited By ~ 3

Author(s):

Kecheng Zhou ◽

Jie Chen ◽

Jiayu Wu ◽

Yangxinzi Xu ◽

Qiaoyun Wu ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Signaling Pathway ◽

Neck Cancer ◽

Molecular Mechanisms ◽

Xenograft Model ◽

Migration And Invasion ◽

Mouse Xenograft Model ◽

Proliferation And Metastasis

Profilin 2 (PFN2) was found to be mainly expressed in neurons and involved in the development of the brain. In recent years, emerging evidence indicated that PFN2 is also significantly upregulated in various cancers including head and neck cancer (HNSC) and influences cancer cell proliferation, migration, and invasion. However, the role of PFN2 in HNSC development and progression remains unclear. The aim of our study was to investigate the role of PFN2 in the development of HNSC and its possible molecular mechanisms. Bioinformatics showed that increased expression of PFN2 in tumors correlated highly with poor prognosis of HNSC patients. Our results indicated that PFN2 was highly expressed in HNSC tissues and in HNSC cell lines. Knockdown of PFN2 inhibited proliferation, invasion, and migration of HNSC cells, while PFN2 overexpression produced the opposite effects. Using a nude mouse xenograft model, we substantiated the tumor-promoting effect of PFN2 on HNSC in vivo. Furthermore, we found that PFN2 downregulation reduced the phosphorylation of Akt and GSK-3β and reduced the expression of β-catenin in HNSC cells. The opposite was observed when PFN2 was overexpressed. Collectively, these results suggest that PFN2 promotes the proliferation and metastasis of HNSC by activating the PI3K/Akt/β-catenin signaling pathway. Although further validation is needed, we speculate that PFN2 plays a crucial role in HNSC and may be a promising therapeutic target and prognostic biomarker.

Download Full-text

Super-Enhancer-Associated TMEM44-AS1 Aggravated Glioma Progression by Forming a Positive Feedback Loop With Myc

10.21203/rs.3.rs-673534/v1 ◽

2021 ◽

Author(s):

Erbao Bian ◽

Xueran Chen ◽

Li Cheng ◽

Meng Cheng ◽

Zhigang Chen ◽

...

Keyword(s):

Positive Feedback ◽

Colony Formation ◽

Feedback Loop ◽

Xenograft Model ◽

Glioma Cells ◽

Migration And Invasion ◽

Positive Feedback Loop ◽

Mouse Xenograft ◽

Super Enhancer ◽

Mouse Xenograft Model

Abstract BackgroundLong non-coding RNAs (lncRNAs) have been considered as one type of gene expression regulator for cancer development, but it is not clear how these are regulated. This study aimed to identify a specific lncRNA that promotes the glioma progression.MethodsRNA sequencing (RNA-seq) and quantitative real-time PCR were performed to screen differentially expressed genes. CCK-8, transwell migration, invasion assays and a mouse xenograft model were performed to determine the functions of TMEM44-AS1. Co-IP, ChIP, Dual-luciferase reporter assays, RNA pulldown and RNA immunoprecipitation assays were performed to study the molecular mechanism of TMEM44-AS1 and the downstream target.ResultsWe identified a novel lncRNA TMEM44-AS1, which was aberrantly expressed in glioma tissues, and that increased TMEM44-AS1 expression was correlated with malignant progression and poor survival for patients with glioma. Expression of TMEM44-AS1 increased the proliferation, colony formation, migration, and invasion of glioma cells. Knockdown of TMEM44-AS1 in glioma cells reduced cell proliferation, colony formation, migration and invasion, and tumor growth in a nude mouse xenograft model. Mechanistically, TMEM44-AS1 is directly bound to the SerpinB3, and sequentially activated Myc signaling; Myc transcriptionally induced TMEM44-AS1 and directly bound to the promoter and super-enhancer of TMEM44-AS1, thus forming a positive feedback loop with TMEM44-AS. Further studies demonstrated that Myc interacts with MED1 regulates the super-enhancer of TMEM44-AS1. More importantly, a novel small-molecule Myc inhibitor, Myci975, alleviated TMEM44-AS1-promoted the growth of glioma cells. Finally, TMEM44-AS1 activated IL-6 signaling by recruiting EGR1 to the promoter of IL-6 in glioma cells. ConclusionsOur study implicates a crucial role of the TMEM44-AS1-Myc axis in glioma progression and provides a possible anti-glioma therapeutic agent.

Download Full-text

7 CHEMOTHERAPEUTIC ACTIVITY OF S-NITROSO-GLUTATHIONE ALONE AND IN COMBINATION WITH CISPLATIN AND RADIATION IN HEAD AND NECK CANCER CELLS AND MOUSE XENOGRAFT MODEL

Radiotherapy and Oncology ◽

10.1016/s0167-8140(12)70001-4 ◽

2012 ◽

Vol 102 ◽

pp. S1

Author(s):

A. Sharma ◽

K. Kolanjiappan ◽

D. McDonald ◽

C. Yount ◽

I. Singh

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Cancer Cells ◽

Neck Cancer ◽

Xenograft Model ◽

Mouse Xenograft ◽

Mouse Xenograft Model ◽

Chemotherapeutic Activity

Download Full-text

The potential of the nude mouse xenograft model for the study of head and neck cancer

Archives of Oto-Rhino-Laryngology ◽

10.1007/bf00454264 ◽

1984 ◽

Vol 239 (1) ◽

pp. 69-79 ◽

Cited By ~ 55

Author(s):

B. J. M. Braakhuis ◽

G. Sneeuwloper ◽

G. B. Snow

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Nude Mouse ◽

Neck Cancer ◽

Xenograft Model ◽

Mouse Xenograft ◽

Mouse Xenograft Model

Download Full-text

CCL2/EGF positive feedback loop between cancer cells and macrophages promotes cell migration and invasion in head and neck squamous cell carcinoma

Oncotarget ◽

10.18632/oncotarget.13523 ◽

2016 ◽

Vol 7 (52) ◽

pp. 87037-87051 ◽

Cited By ~ 18

Author(s):

Lu Gao ◽

Feng-qin Wang ◽

Hui-min Li ◽

Jie-gang Yang ◽

Jian-Gang Ren ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Migration ◽

Cell Carcinoma ◽

Head And Neck ◽

Cancer Cells ◽

Squamous Cell ◽

Positive Feedback ◽

Feedback Loop ◽

Migration And Invasion ◽

Positive Feedback Loop

Download Full-text

THAP9-AS1/miR-133b/SOX4 positive feedback loop facilitates the progression of esophageal squamous cell carcinoma

Cell Death and Disease ◽

10.1038/s41419-021-03690-z ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Jiwei Cheng ◽

Haibo Ma ◽

Ming Yan ◽

Wenqun Xing

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Positive Feedback ◽

Feedback Loop ◽

Malignant Tumors ◽

Migration And Invasion ◽

Positive Feedback Loop

AbstractEsophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in the digestive system with a high incidence and poor prognosis. Long non-coding RNAs (LncRNA) have been reported to be closely associated with the occurrence and development of various human cancers. Data from GSE89102 shows an increase of THAP9-AS1 expression in ESCC. However, its functions and mechanisms underlying ESCC progression remain to be investigated. In this study, we found that THAP9-AS1 was overexpressed in ESCC tissues and cells. High THAP9-AS1 expression was positively correlated with tumor size, TNM stage, lymph node metastasis, and worse prognosis. Functionally, depletion of THAP9-AS1 suppressed cell proliferation, migration, and invasion, while enhanced apoptosis in vitro. Consistently, knockdown of THAP9-AS1 inhibited xenograft tumor growth in vivo. Mechanistically, THAP9-AS1 could serve as a competing endogenous RNA (ceRNA) for miR-133b, resulting in the upregulation of SOX4. Reciprocally, SOX4 bound to the promoter region of THAP9-AS1 to activate its transcription. Moreover, the anti-tumor property induced by THAP9-AS1 knockdown was significantly impaired due to miR-133b downregulation or SOX4 overexpression. Taken together, our study reveals a positive feedback loop of THAP9-AS1/miR-133b/SOX4 to facilitate ESCC progression, providing a potential molecular target to fight against ESCC.

Download Full-text