Overexpression of HOXB7 protein reduces sensitivity of oral cancer cells to chemo-radiotherapy

Zhang, Yuan; Chen, D; Chen, Xin; Hai-tao, Yang; Wei, Yaming

doi:10.1038/cgt.2016.55

Cited by 13 publications

(13 citation statements)

References 31 publications

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“…Another research suggested that Wnt signaling was also involved in TGF-␤-mediated fibrosis (57). Similarly, HOXB7 overexpression advanced oral cancer cell migration via the activation of the transforming growth factor ␤2/SMAD3 signaling pathway (54). This supporting evidence and reported studies offer the basis in demonstrating the possible link between both HOXB7 and the Wnt/␤-catenin signaling pathway.…”

Section: Discussionmentioning

confidence: 61%

Specific knockdown of HOXB7 inhibits cutaneous squamous cell carcinoma cell migration and invasion while inducing apoptosis via the Wnt/β-catenin signaling pathway

Gao

Chen

2018

American Journal of Physiology-Cell Physiology

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Metastatic cutaneous squamous cell carcinoma (CSCC) is a major cause of death associated with non-melanoma skin cancer. The involvement of homeobox B7 (HOXB7) in cancers has been reported. Thus, the current study intends to explore the effect of HOXB7 on CSCC and its relationship with the Wnt/β-catenin signaling pathway. Initially, microarray-based gene expression profiling of CSCC was performed and HOXB7 was identified as an upregulated gene based on the microarray data of GSE2068. Following this, the experimental results indicated that HOXB7 and β-catenin formed a composite, demonstrating that endogenous HOXB7 binds to β-catenin. Subsequently, CSCC cells were treated with siRNA against HOXB7 or inhibitor of Wnt/β-catenin signaling pathway (IWR-1) in order to analyze any underlying regulatory mechanism of HOXB7 on the CSCC cells. Tumor growth involving xenografts in nude mice was also observed so as to explore whether or not HOXB7 could regulate subcutaneous tumor growth through in vivo culturing. In order to investigate the potential effects of HOXB7 on the Wnt/β-catenin signaling pathway, we determined the expression of HOXB7 and downstream genes of the Wnt/β-catenin signaling pathway. Notably, siRNA-mediated knockdown of HOXB7 inhibited the activation of the Wnt/β-catenin signaling pathway, thereby impeding the progression of cell viability, migration, and invasion as well as of the tumor growth, while contrarily facilitating cell apoptosis. Taken together, silencing of the HOXB7 has the mechanism of inactivating the Wnt/β-catenin signaling pathway, thereby accelerating cell apoptosis and suppressing cell migration and invasion in CSCC, which could provide a candidate target for the CSCC treatment.

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Section: Discussionmentioning

confidence: 61%

Specific knockdown of HOXB7 inhibits cutaneous squamous cell carcinoma cell migration and invasion while inducing apoptosis via the Wnt/β-catenin signaling pathway

Gao

Chen

2018

American Journal of Physiology-Cell Physiology

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“…Homeobox B7 (HOXB7) has been reported to be aberrantly expressed in a variety of cancers, including melanoma [9], breast cancer [10–15], gastric cancer [16, 17], liver cancer [18, 19], colorectal cancer [20] and esophageal cancer [21]. In addition, its expression has been correlated with clinical progression and poor outcome and may serve as a potential prognostic factor and therapeutic target [11, 14, 19, 20, 22, 23]. HOXB7 is involved in many of the major cellular processes that occur in cancer, including proliferation, invasion, migration, angiogenesis and the epithelial–mesenchymal transition (EMT) [24].…”

Section: Introductionmentioning

confidence: 99%

Upregulated expression of HOXB7 in intrahepatic cholangiocarcinoma is associated with tumor cell metastasis and poor prognosis

Dai

Yang

et al. 2019

Laboratory Investigation

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Homeobox B7 (HOXB7) protein is reported to be aberrantly expressed in a variety of cancers and to play an important role in multiple cellular processes. However, the specific mechanism by which HOXB7 promotes the malignant progression of intrahepatic cholangiocarcinoma (ICC) remains unclear. Therefore, we used quantitative real-time polymerase chain reaction (PCR) to detect the expression level of HOXB7 in 38 paired ICC tissue samples. Additionally, to assess correlation between HOXB7 and ICC prognosis, we performed immunohistochemistry (IHC) using 122 ICC tissues to detect HOXB7 expression. Cell Counting Kit-8 (CCK-8) and colony formation assays were employed to assess ICC cell proliferation, and Transwell assays were performed to estimate the invasion and migration abilities of ICC cells. The capillary tube formation assay was applied to explore the angiogenic effects of HOXB7. A xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth and lung metastasis. The results showed higher expression of HOXB7 in ICC tissues than in noncancerous tissues, and this increased expression was significantly associated with a poor prognosis. In addition, HOXB7 overexpression enhanced capillary tube formation, invasion and migration of ICC cells in vitro, whereas HOXB7 knockdown produced the opposite results in vitro. Moreover, the role of HOXB7 in promoting tumor growth and metastasis was verified in vivo. Further investigation revealed that the expression levels of MMP2, MMP9, VEGFa, and IL8 were elevated by HOXB7 and that the ERK pathway was activated. Our results demonstrate the prognostic value of HOXB7 and its role in metastasis and angiogenesis in ICC. HOXB7 upregulated MMP2, MMP9, VEGFa, and IL8 expression via the ERK pathway to accelerate the malignant progression of ICC.

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“…12 Overexpression of HOXB7 decreased the sensitivity of oral cancer cells to vincristine-induced apoptosis. 13 HOXB13 confers Tamoxifen resistance by directly downregulating ERa transcription and inducing IL-6 expression. 14 Previously, we found that HOXB7 was overexpressed in ESCC tissues compared with paired noncancerous mucosa, and it promoted oncogenic properties in ESCC cells through affecting cell proliferation, cell cycle and cell apoptosis, and presented negative survival significance in ESCC patients.…”

Section: Introductionmentioning

confidence: 99%

“…Knockdown of HOXC6 expression in multidrug resistance cells increased their sensitivity to paclitaxel via its regulation of MDR‐1 12 . Overexpression of HOXB7 decreased the sensitivity of oral cancer cells to vincristine‐induced apoptosis 13 . HOXB13 confers Tamoxifen resistance by directly downregulating ERa transcription and inducing IL‐6 expression 14 .…”

Section: Introductionmentioning

confidence: 99%

HOXB7 mediates cisplatin resistance in esophageal squamous cell carcinoma through involvement of DNA damage repair

Zhou

Dong

et al. 2019

Thoracic Cancer

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Background DNA damage repair is an important mechanism of platinum resistance. HOXB7 is one member of HOX family genes, which are essential developmental regulators and frequently dysregulated in cancer. Recently, its relevance in chemotherapy resistance and DNA damage repair has also been addressed. However, little is known regarding the association between HOXB7 and chemotherapy resistance in esophageal squamous cell carcinoma (ESCC). Methods The association between HOXB7 expression detected by immunohistochemisty and tumor regression grade (TRG) and long‐term survival was analyzed in 143 ESCC patients who underwent neoadjuvant chemotherapy. CCK8 assay was used to examine the effect of cisplatin in a panel of four ESCC cell lines. A stable cell strain with HOXB7 knockdown of KYSE150 and KYSE450 was established to explore the effect on cisplatin sensitivity. The interaction of HOXB7 with Ku70, Ku80 and DNA‐PKcs was determined by GST‐pull down, coimmunoprecipitation and immunofluorescent colocalization. Finally, we investigated whether disrupting HOXB7 function by a synthetic peptide HXR9 blocking the formation of HOXB7/PBX could enhance cisplatin sensitivity in vitro and in vivo. Results High expression of HOXB7 was associated with cisplatin resistance and worse chemotherapy efficacy. HOXB7 knockdown reinforced cisplatin sensitivity. It was identified that HOXB7 interacts with Ku70, Ku80 and DNA‐PKcs. HOXB7 knockdown was related to the downregulation of Ku70, Ku80 and DNA‐PKcs as well as arrested cell cycle in S phase. HOXB7 inhibition by HXR9 had a synergistic effect to improve cisplatin sensitivity. Conclusion HOXB7 may be a biomarker for the prediction of chemoresistance of ESCC and serves as a promising therapeutic target.

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Overexpression of HOXB7 protein reduces sensitivity of oral cancer cells to chemo-radiotherapy

Cited by 13 publications

References 31 publications

Specific knockdown of HOXB7 inhibits cutaneous squamous cell carcinoma cell migration and invasion while inducing apoptosis via the Wnt/β-catenin signaling pathway

Specific knockdown of HOXB7 inhibits cutaneous squamous cell carcinoma cell migration and invasion while inducing apoptosis via the Wnt/β-catenin signaling pathway

Upregulated expression of HOXB7 in intrahepatic cholangiocarcinoma is associated with tumor cell metastasis and poor prognosis

HOXB7 mediates cisplatin resistance in esophageal squamous cell carcinoma through involvement of DNA damage repair

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