Claudin-7 Inhibits Proliferation and Metastasis in Salivary Adenoid Cystic Carcinoma Through Wnt/β-Catenin Signaling

Huan, Jun; Ding, Xu; Zhang, Wei; Zheng, Yang; Du, Hongming; Zheng, Yujie; Song, Hongcheng; Li, Meng; Jiang, Yue; Xie, Jiaxiang; Wu, Ming; Jiao, Pengfei; Wang, Zeyu; Wu, Heming; Zhong, Yi

doi:10.1177/0963689720943583

Cited by 15 publications

(11 citation statements)

References 28 publications

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“…We found that CLDN6 overexpression inhibited mRNA and protein expression of c–MYC and target glycolytic genes GLUT1 and LDHA . Similarly, Ji H et al [ 38 ] found that CLDN7 knockdown increased the c–MYC protein expression in salivary adenoid cystic carcinoma, and Che J et al [ 39 ] found that overexpression of CLDN3 reduced c–MYC expression.…”

Section: Discussionmentioning

confidence: 98%

CLDN6 Suppresses c–MYC–Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer

Wang

et al. 2021

IJMS

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Claudin 6 (CLDN6) was found to be a breast cancer suppressor gene, which is lowly expressed in breast cancer and inhibits breast cancer cell proliferation upon overexpression. However, the mechanism by which CLDN6 inhibits breast cancer proliferation is unclear. Here, we investigated this issue and elucidated the molecular mechanisms by which CLDN6 inhibits breast cancer proliferation. First, we verified that CLDN6 was lowly expressed in breast cancer tissues and that patients with lower CLDN6 expression had a worse prognosis. Next, we confirmed that CLDN6 inhibited breast cancer proliferation through in vitro and in vivo experiments. As for the mechanism, we found that CLDN6 inhibited c–MYC–mediated aerobic glycolysis based on a metabolomic analysis of CLDN6 affecting cellular lactate levels. CLDN6 interacted with a transcriptional co–activator with PDZ-binding motif (TAZ) and reduced the level of TAZ, thereby suppressing c–MYC transcription, which led to a reduction in glucose uptake and lactate production. Considered together, our results suggested that CLDN6 suppressed c–MYC–mediated aerobic glycolysis to inhibit the proliferation of breast cancer by TAZ, which indicated that CLDN6 acted as a novel regulator of aerobic glycolysis and provided a theoretical basis for CLDN6 as a biomarker of progression in breast cancer.

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Section: Discussionmentioning

confidence: 98%

CLDN6 Suppresses c–MYC–Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer

Wang

et al. 2021

IJMS

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“…Conversely, CLDN7 is notably elevated in cervical and gastric cancer ( 23 , 24 ). CLDN7 suppresses proliferation and metastasis in salivary adenoid cystic carcinoma ( 9 ). Of note, loss of CLDN7 expression may be associated with the pathogenesis of OSCC and this loss is associated with a poor prognosis ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

“…An increasing number of studies have confirmed that the abnormal expression of CLDN7 can disrupt the integrity of tight junctions, thereby resulting in the loss of cell polarity, and inducing abnormal proliferation, invasion and metastasis ( 6 , 7 ). Accumulating evidence has shown that CLDN7 is abnormally expressed in multiple types of cancer tissues, such as ovarian carcinoma, salivary adenoid cystic carcinoma and colorectal cancer ( 6 , 8 , 9 ), indicating that alterations in CLDN7 expression may be closely related to the occurrence of these tumors. Emerging evidence supports the notion that low expression of CLDN7 serves as a crucial feature of OSCC, and loss of CLDN7 is considered as a negative prognostic factor for invasion and metastasis in OSCC ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

IRF2‑induced Claudin‑7 suppresses cell proliferation, invasion and migration of oral squamous cell carcinoma

Yang

2021

Exp Ther Med

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Oral squamous cell carcinoma (OSCC) is a common type of malignant tumor worldwide. Claudin-7 (CLDN7) has been reported to exhibit low expression in tissues of patients with OSCC; however, the underlying mechanisms of CLDN7 remain to be elucidated. The present study aimed to investigate the effects of CLDN7 on the progression of OSCC and identify its potential regulatory mechanisms. CLDN7 and interferon regulatory factor-2 (IRF2) expression in several OSCC cell lines were detected using reverse transcription-quantitative PCR (RT-qPCR) and western blotting. Following CLDN7 overexpression, cell proliferation, invasion and migration were determined using a Cell Counting Kit-8, colony formation, Transwell and wound healing assays, respectively. The potential binding sites of IRF2 on the CLDN7 promoter were analyzed using the PROMO and JASPAR databases, which were verified via chromatin immunoprecipitation and RT-qPCR assays. The effects of IRF2 and CLDN7 on the biological functions of OSCC cells were examined by transfection with short hairpin RNA (shRNA) against CLDN7 (sh-CLDN7), or IRF2 and CLDN7 overexpression plasmids. The results revealed that CLDN7 and IRF2 expression were significantly downregulated in OSCC cell lines, and CLDN7 overexpression reduced the proliferation, invasion and migration of OSCC cells. Additionally, IRF2 was confirmed to combine with the CLDN7 promoter. CLDN7 silencing reversed the inhibitory effects of IRF2 overexpression on the proliferation, invasion and migration of OSCC cells. Taken together, these findings demonstrated that IRF2-induced CLDN7 upregulation suppressed the proliferation, invasion and migration of OSCC cells, suggesting the possibility of CLDN7 and IRF2 as novel targets for the treatment of OSCC.

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“…The procedure of immunohistochemistry (IHC) was carried out as we described previously [25]. The stained slides were analyzed by two pathologists separately.…”

Section: Immunohistochemistry and Evaluation Of Immunoreactivitymentioning

confidence: 99%

“…Real-time RT-PCR and western blotting assays were carried out in accordance with standard process as we described previously [25]. Nuclear and cytoplasmic protein extraction from cells is in accordance with the TRIZOL reagent (Invitrogen) manufacturer's protocol.…”

Section: Real-time Pcr and Western Blotting Assaysmentioning

confidence: 99%

FAM83A promotes proliferation and metastasis via Wnt/β-catenin signaling in head neck squamous cell carcinoma

et al. 2021

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This research aimed to investigate the expression and function of FAM83A in the proliferation and metastasis in head and neck squamous cell carcinoma (HNSCC). FAM83A mRNA and protein expressions in HNSCC were detected in primary HNSCC samples and cell lines. The associations between FAM83A expression and clinicopathologic variables were evaluated through tissue microarrays. Besides, FAM83A knockdown and overexpression cell lines were constructed to assess cell growth and metastasis in vitro and the relationship between FAM83A and epithelial-mesenchymal transition (EMT). Furthermore, two models of xenograft tumors in nude mice were used to assess the tumorigenicity and metastasis ability of FAM83A in vivo. In the present study, overexpression of FAM83A in HNSCC samples was significantly associated with tumor size, lymph node status and clinical tumor stages. Mechanically, FAM83A could promote HNSCC cell growth and metastasis by inducing EMT via activating Wnt/β-catenin signaling pathway. Rescue experiment demonstrated the inhibition of β-catenin could counteract the function of FAM83A. Also, the FAM83A knockdown could suppress tumor growth and distant metastasis in the xenograft animal models of HNSCC. In conclusion, this study identifies FAM83A as an oncogene of HNSCC. This study provides new insights into the molecular pathways that contribute to EMT in HNSCC. We revealed a previously unknown FAM83A-Wnt–β-catenin signaling axis involved in the EMT of HNSCC. There may be a potential bi-directional signaling loop between FAM83A and Wnt/β-catenin signaling pathway in HNSCC.

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Claudin-7 Inhibits Proliferation and Metastasis in Salivary Adenoid Cystic Carcinoma Through Wnt/β-Catenin Signaling

Cited by 15 publications

References 28 publications

CLDN6 Suppresses c–MYC–Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer

CLDN6 Suppresses c–MYC–Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer

IRF2‑induced Claudin‑7 suppresses cell proliferation, invasion and migration of oral squamous cell carcinoma

FAM83A promotes proliferation and metastasis via Wnt/β-catenin signaling in head neck squamous cell carcinoma

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