B7-Homolog 4 Promotes Epithelial‐Mesenchymal Transition and Invasion of Bladder Cancer Cells via Activation of Nuclear Factor-κB

Wu, Haoran; Wang, Xugang; Mo, Naixin; Zhang, Liang; Yuan, Xiaoliang; Lü, Zhong

doi:10.3727/096504018x15172227703244

Cited by 12 publications

(8 citation statements)

References 24 publications

(18 reference statements)

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“…For example, B7-H4 upregulation induces immune escape of lung cancer [ 42 ] and non-small cell lung cancer cells [ 43 ] through MEK/ERK and PD-1/Stat3 signaling pathways. B7-H4 overexpression promotes the metastasis of bladder cancer cells through Nuclear Factor-kappa B signaling [ 44 ]. However, the mechanism by which B7-H4 promotes the migration of CRC cells remains unknown.…”

Section: Discussionmentioning

confidence: 99%

B7 family member H4 induces epithelial-mesenchymal transition and promotes the proliferation, migration and invasion of colorectal cancer cells

et al. 2021

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Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract, which has the second highest incidence among gastrointestinal tumors. At present, due to the limitations of current CRC treatment strategies, there is an urgent need for developing more effective therapies. B7 family member H4 (B7-H4) is associated with the progression of a wide spectrum of cancers, but its functional role in CRC is unknown. The purpose of this study is to clarify the role of B7-H4 in CRC and the underlying mechanisms in controlling the progression of CRC. Our data showed that B7-H4 expression in CRC tissues and cell lines was significantly upregulated as compared with normal tissues and normal cell lines. High B7-H4 expression was correlated with a poor prognosis of CRC patients. B7-H4 overexpression promoted the proliferation and invasion of CRC cells, which could be suppressed by Wnt signaling inhibitor. In a mouse xenograft model, silencing B7-H4 suppressed tumor growth and epithelial–mesenchymal transition (EMT) of CRC cells. Collectively, our study demonstrated the oncogenic roles of B7-H4 in regulating the proliferation, EMT as well as the migration of CRC cells through Wnt signaling pathway. The heightened expression of B7-H4 could serve as a prognostic marker for CRC patients.

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Section: Discussionmentioning

confidence: 99%

B7 family member H4 induces epithelial-mesenchymal transition and promotes the proliferation, migration and invasion of colorectal cancer cells

et al. 2021

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“…For instance, PD-L1 has been confirmed to be an important mediator of EMT in certain human cancer tissues, such as lung cancer, colorectal cancer, esophageal cancer, and head and neck cancer [28, 40–42]. Moreover, other members such as B7-H3 and B7-H4, have also been suggested to promote EMT of cancer cells during cancer progression [43–45].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of HHLA2 in human clear cell renal cell carcinoma is significantly associated with poor survival of the patients

et al. 2019

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Background It is well known that human clear cell renal cell carcinoma (ccRCC) is a highly immunogenic and chemo-resistant tumor. Recently, emerging data suggest that the immune checkpoint blockade therapy is an important breakthrough in the treatment against ccRCC. HHLA2, a recently reported member of B7 family, is uniquely expressed in humans but not in mice, and it plays an important role in the functional inhibition of CD4 and CD8 T cells. Herein, we aimed to study the clinical implications of HHLA2 expression in human ccRCC and its potential regulatory role in the biological functions of the cancer cells. Methods In the present study, we examined HHLA2 expression in human ccRCC tissues and analyzed the clinical implications as well as prognostic value. The intervention of HHLA2 in human ccRCC cell lines ACHN and 786-O was performed and its effect on the cellular function of the cells was also analyzed. We also identified the differentially expressed genes upon HHLA2 knockdown in ccRCC cell lines by using gene microarray analysis. Results We found that higher HHLA2 mRNA expression level in human ccRCC tissues compared with that in adjacent normal tissues based on TCGA data, and the HHLA2 expression at mRNA level was positively and significantly correlated with PD-L1, PD-L2, B7-H6, but negatively and significantly correlated with B7-H3. Moreover, our immunohistochemistry study showed that the staining intensity of HHLA2 in human ccRCC tissues was significantly higher than that in the adjacent normal tissues, and the overall survival rate of ccRCC patients with higher HHLA2 expression was significantly poorer than that of the patients with lower HHLA2 expression. Higher expression of HHLA2 in ccRCC tissues was positively and significantly associated with larger tumor size and advanced TNM stage. The COX model revealed that the parameters including patient’s age, TNM stage and HHLA2 expression level could be used as the independent risk factors respectively for the prognostic prediction of the patients. Our cellular study showed that upon knockdown of HHLA2 expression in human ccRCC cell lines, the cell viability, the migration and the invasion ability were significantly inhibited, while the cell cycle arrest at G1 phase was induced and the expressions of Cyclin D1, c-Myc and Cyclin E1 were decreased. In addition, according to the microarray data, the expressions of epithelia-to-mesenchymal transition markers, such as E-cadherin, N-cadherin and Vimentin, were significantly changed after knockdown of HHLA2 expression. Conclusions Our findings indicated that HHLA2 was involved in the progression of human ccRCC and could be used as an important prognostic predictor for this malignancy.

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“…B7-H3 and B7-H4 (VTCN1) belong to a family of immune modulators that includes PD-L1 (B7-H1) and are regarded as a promising molecular target for immunocheckpoint therapy [24]. In fact, many preclinical studies reported the possible effectiveness of B7-H3- or B7-H4-targeting antibody, among the B7 family, in the treatment of cancers [25,26,27,28,29]. Furthermore, since we would like to elevate our study to translational research, we focused on B7-H3 and B7-H4, which are currently being tested in a clinical trial [30,31,32].…”

Section: Discussionmentioning

confidence: 99%

Genomic Characteristics of Invasive Mucinous Adenocarcinomas of the Lung and Potential Therapeutic Targets of B7-H3

Nakagomi

Goto

Hirotsu

et al. 2018

Cancers

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Pulmonary invasive mucinous adenocarcinoma (IMA) is considered a variant of lung adenocarcinomas based on the current World Health Organization classification of lung tumors. However, the molecular mechanism driving IMA development and progression is not well understood. Thus, we surveyed the genomic characteristics of IMA in association with immune-checkpoint expression to investigate new potential therapeutic strategies. Tumor cells were collected from surgical specimens of primary IMA, and sequenced to survey 53 genes associated with lung cancer. The mutational profiles thus obtained were compared in silico to conventional adenocarcinomas and other histologic carcinomas, thereby establishing the genomic clustering of lung cancers. Immunostaining was also performed to compare expression of programmed death ligand 1 (PD-L1) and B7-H3 in IMA and conventional adenocarcinomas. Mutations in Kirsten rat sarcoma viral oncogene homolog (KRAS) were detected in 75% of IMAs, but in only 11.6% of conventional adenocarcinomas. On the other hand, the frequency of mutations in epidermal growth factor receptor (EGFR) and tumor protein p53 (TP53) genes was 5% and 10%, respectively, in the former, but 48.8% and 34.9%, respectively, in the latter. Clustering of all 78 lung cancers indicated that IMA is distinct from conventional adenocarcinoma or squamous cell carcinoma. Strikingly, expression of PD-L1 in ≥1% of cells was observed in only 6.1% of IMAs, but in 59.7% of conventional adenocarcinomas. Finally, 42.4% and 19.4% of IMAs and conventional adenocarcinomas, respectively, tested positive for B7-H3. Although currently classified as a variant of lung adenocarcinoma, it is also reasonable to consider IMA as fundamentally distinct, based on mutation profiles and genetic clustering as well as immune-checkpoint status. The immunohistochemistry data suggest that B7-H3 may be a new and promising therapeutic target for immune checkpoint therapy.

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B7-Homolog 4 Promotes Epithelial‐Mesenchymal Transition and Invasion of Bladder Cancer Cells via Activation of Nuclear Factor-κB

Cited by 12 publications

References 24 publications

B7 family member H4 induces epithelial-mesenchymal transition and promotes the proliferation, migration and invasion of colorectal cancer cells

B7 family member H4 induces epithelial-mesenchymal transition and promotes the proliferation, migration and invasion of colorectal cancer cells

Overexpression of HHLA2 in human clear cell renal cell carcinoma is significantly associated with poor survival of the patients

Genomic Characteristics of Invasive Mucinous Adenocarcinomas of the Lung and Potential Therapeutic Targets of B7-H3

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