Wnt7a predicts poor prognosis, and contributes to growth and metastasis in tongue squamous cell carcinoma

Abstract

Regional and distant metastases are the principal reasons underlying the high mortality rate associated with tongue squamous cell carcinoma (TSCC); however, the precise molecular mechanisms involved in tongue tumorigenesis remain unknown. The present study aimed to determine the expression and mechanism of regulation of Wnt7a in the growth and metastasis of TSCC. Wnt7a mRNA and protein expression levels were examined in TSCC tissues using reverse transcription-quantitative polymerase chain reaction and immunohistochemical staining. A loss-of-function assay was performed in TSCC cell lines using Wnt7a small interfering RNA or short hairpin RNA, after which, cell proliferation, migration and invasion were analyzed using Cell Counting Kit-8, tumorigenicity and Transwell assays, respectively. Epithelial-mesenchymal transition (EMT)-associated proteins were detected by western blotting. The mRNA and protein expression levels of Wnt7a were significantly upregulated in cancer tissues compared with in the adjacent non-cancerous tissues. Clinical analysis indicated that Wnt7a expression was associated with T classification, lymph node metastasis and pathological differentiation, and high Wnt7a expression predicted a short recurrence-free survival for patients with TSCC. Silencing Wnt7a expression suppressed cell proliferation, migration and invasion, and reversed the EMT phenotype in TSCC cell lines. The present study revealed that Wnt7a may be upregulated in TSCC, where it may participate in modulating cell proliferation, migration, invasion and the EMT of TSCC. Therefore, Wnt7a should be considered a novel oncogene, and a potential prognostic and therapeutic target for patients with TSCC.

Compressed phenotypic screens for complex multicellular models and high-content assays

“…As stated above, we annotated the type 2 immunity GEP based on its association with IL-4 and IL-13, as well as ADIPOQ, in both compressed screens. Reassuringly, we found that IFN-γ was associated with the IFN-γ response GEP, IFN-α2 was associated with the type I IFN signaling GEP, TGF-β and INHBB (a member of the TGF-β superfamily) with the TGF-β response GEP, IL-1A, IL-1B, and TNF-α (known activators of NF-κβ 26 ) with the NF-κβ activation GEP, and the mitogens WNT7A and RSPO3 were associated with the ribosomal GEP 27,28 .…”

“…As stated above, we annotated the type 2 immunity GEP based on its association with IL-4 and IL-13, as well as ADIPOQ, in both compressed screens. Reassuringly, we found that IFN-γ was associated with the IFN-γ response GEP, IFN-ɑ2 was associated with the type I IFN signaling GEP, TGF-β and INHBB (a member of the TGF-β superfamily) with the TGF-β response GEP, IL-1A, IL-1B, and TNF-α (known activators of NF-κβ 26 ) with the NF-κβ activation GEP, and the mitogens WNT7A and RSPO3 were associated with the ribosomal GEP 27,28 . Interestingly, we would not have been able to infer which ligands were most active in the organoids by examining cognate receptor expression, given our active ligands spanned the range of cognate receptor expression in negative control organoid cells (Extended Data Fig.…”

Controlled Fabrication of Bioactive Microtubes for Screening Anti-Tongue Squamous Cell Migration Drugs

“…The 5-years survival rate of advanced TSCC is approximately 50% (Fan et al, 2018). In addition, there are currently no effective drugs available to treat TSCC in situ and inhibit the distant metastases in the early stage (Jia B. et al, 2019). Therefore, it is urgent to experimentally screen out drugs that effectively inhibit the invasion and metastasis of TSCC, which could be applied clinically to prevent tumors to spread and improve the survival rate of patients eventually (Fan et al, 2018).…”

LncRNA GACAT1 induces tongue squamous cell carcinoma migration and proliferation via miR‐149

“…Tongue squamous cell carcinoma (TSCC) represents the most frequent type of oral squamous cell carcinoma (OSCC) and is famous for its high potential of metastasis and proliferation 1‐5 . TSCC usually leads to speech, deglutition and mastication malfunction 6‐8 . Despite the advancement in radiotherapy, chemotherapy and surgery, the 5‐year survival rate of this disease is still not satisfactory 9‐12 .…”

“…Despite the advancement in radiotherapy, chemotherapy and surgery, the 5‐year survival rate of this disease is still not satisfactory 9‐12 . Survival rate improvement requires more understanding of initiation and progression of TSCC 6,13,14 . Therefore, more works should be performed to explain the molecular mechanisms and process, which may identify new effective targets for TSCC treatment.…”