HOXB5 acts as an oncogenic driver in head and neck squamous cell carcinoma via EGFR/Akt/Wnt/β-catenin signaling axis

Lee, Kyung-Min; Chang, Jae Won; Oh, Chahyun; Liu, Lihua; Jung, Seung-Hyun; Won, Ho-Ryun; Kim, Young Il; Rha, Ki-Sang; Koo, Bon Seok

doi:10.1016/j.ejso.2019.12.009

Cited by 29 publications

(34 citation statements)

References 35 publications

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“…The research works have demonstrated that FGFR4 can promote HNSCC metastasis via EGFR/Akt/Wnt/β-catenin signaling axis 45 and induce EMT in breast Cancer Cells 21 . Therefore, we intended to detect whether HOXB5 can active β-catenin pathway and induce EMT.…”

Section: Resultsmentioning

confidence: 99%

Homeobox B5 promotes metastasis and poor prognosis in Hepatocellular Carcinoma, via FGFR4 and CXCL1 upregulation

He¹,

Huang²,

Liu³

et al. 2021

Theranostics

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Background: Since metastasis remains the main reason for HCC-associated death, a better understanding of molecular mechanism underlying HCC metastasis is urgently needed. Here, we elucidated the role of Homeobox B5 (HOXB5), a member of the HOX transcriptional factor family, in promoting HCC metastasis. Method: The expression of HOXB5 and its functional targets fibroblast growth factor receptor 4 (FGFR4) and C-X-C motif chemokine ligand 1 (CXCL1) were detected by immunohistochemistry. Luciferase reporter and chromatin immunoprecipitation assays were performed to measure the transcriptional regulation of target genes by HOXB5. The effects of FGFR4 and CXCL1 on HOXB5-mediated metastasis were analyzed by an orthotopic metastasis model. Results: Elevated expression of HOXB5 had a positive correlation with poor tumour differentiation, higher TNM stage, and indicated unfavorable prognosis. Overexpression of HOXB5 promoted HCC metastasis through transactivating FGFR4 and CXCL1 expression, whereas knockdown of FGFR4 and CXCL1 decreased HOXB5-enhanced HCC metastasis. Moreover, HOXB5 overexpression in HCC cells promoted myeloid derived suppressor cells (MDSCs) infiltration through CXCL1/CXCR2 axis. Either depletion of MDSCs by anti-Gr1 or blocking CXCL1-CXCR2 axis by CXCR2 inhibitor impaired HOXB5-mediated HCC metastasis. In addition, fibroblast growth factor 19 (FGF19) contributed to the HOXB5 upregulation through PI3K/AKT/HIF1α pathway. Overexpression of FGF15 (an analog of FGF19 in mouse) promoted HCC metastasis, whereas knockdown of HOXB5 significantly inhibited FGF15-enhanced HCC metastasis in immunocompetent mice. HOXB5 expression was positively associated with CXCL1 expression and intratumoral MDSCs accumulation in human HCC tissues. Patients who co-expressed HOXB5/CXCL1 or HOXB5/CD11b exhibited the worst prognosis. Furthermore, the combination of FGFR4 inhibitor BLU-554 and CXCR2 inhibitor SB265610 dramatically decreased HOXB5-mediated HCC metastasis. Conclusion: HOXB5 was a potential prognostic biomarker in HCC patients and targeting this loop may provide a promising treatment strategy for the inhibition of HOXB5-mediated HCC metastasis.

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Section: Resultsmentioning

confidence: 99%

Homeobox B5 promotes metastasis and poor prognosis in Hepatocellular Carcinoma, via FGFR4 and CXCL1 upregulation

He¹,

Huang²,

Liu³

et al. 2021

Theranostics

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“…Most HNSCC patients have a poor prognosis because of advanced cancer when diagnosed, despite considerable advancements in diagnosis and treatment in recent years [2 , 24] . With intensive studies in the immune molecular mechanisms, precision oncology has become reality for several types of cancers [25 , 26] .…”

Section: Discussionmentioning

confidence: 99%

“…Head and neck squamous cell carcinoma (HNSCC) is the sixth most common global cancer [1] . Nearly 50% patients die annually within the frame of 5-year survival rate, despite considerable advances in diagnosis and treatment in recent years [2 , 3] . Surgery is the first priority of therapeutic regimen , combined with chemotherapy and radiation therapy.…”

Section: Introductionmentioning

confidence: 99%

A signature of 17 immune-related gene pairs predicts prognosis and immune status in HNSCC patients

Jiang

et al. 2021

Translational Oncology

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Highlights We utilized multidimensional bioinformatics methods to validate the robustness of prognostic value for our 17 IRGPs signature and explored the relationship between the IRGPs model and immune status. The low-risk group demonstrated a distinctly favorable prognosis, including OS, DSS, and PFS. Through comparing PD-L1, MSI, and TIDE between high and low risk groups, low-risk group was much more sensitive to immunotherapy. Compared to the high-risk group, the low-risk group demonstrated a distinctly favourable prognosis, and the low-risk group was much more sensitive to immunotherapy. The IRGPs model is an independent biomarker for estimating the prognosis, and could be used to predict immunotherapeutic response in HNSCC patients .

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“…Approximately 50% of patients die annually within the frame of 5-year survival rate [ 1 ]. Most HNSC patients have a poor prognosis because of advanced cancer when diagnosed despite considerable advancements in diagnosis and treatment in recent years [ 2 ]. With intensive studies in the area of molecular mechanisms, precision oncology has become the focus for several types of cancers [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Therapeutic and Prognostic Biomarkers of Lamin C (LAMC) Family Members in Head and Neck Squamous Cell Carcinoma

Jiang

et al. 2020

Med Sci Monit

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HOXB5 acts as an oncogenic driver in head and neck squamous cell carcinoma via EGFR/Akt/Wnt/β-catenin signaling axis

Cited by 29 publications

References 35 publications

Homeobox B5 promotes metastasis and poor prognosis in Hepatocellular Carcinoma, via FGFR4 and CXCL1 upregulation

Homeobox B5 promotes metastasis and poor prognosis in Hepatocellular Carcinoma, via FGFR4 and CXCL1 upregulation

A signature of 17 immune-related gene pairs predicts prognosis and immune status in HNSCC patients

Identification of Therapeutic and Prognostic Biomarkers of Lamin C (LAMC) Family Members in Head and Neck Squamous Cell Carcinoma

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