Decreased expression of 14‐3‐3 σ, an early event of malignant transformation of respiratory epithelium, also facilitates progression of squamous cell lung cancer

Abstract

BackgroundIt has been shown that 14-3-3 σ serves as a tumor suppressor gene, and is downregulated in various tumor tissues. However, the role of 14-3-3 σ during the initiation and progression of lung squamous cell carcinoma (SqCC) is not well understood.MethodsThe expression status of 14-3-3 σ in archival tissue samples from 40 lung SqCC patients (36 with normal bronchia, 19 squamous metaplasia, and 17 dysplasia/carcinoma in situ, in their tissue samples) was examined by immunohistochemical analysis. The proliferation rate and tumor formation ability of the H520 cell transfected with 14-3-3 σ was tested with methyl thiazolyl tetrazolium assay and nude mice subcutaneous injection, respectively.ResultsIn the normal bronchial epithelia, 14-3-3 σ was highly expressed, whereas it was significantly decreased in precancerous and cancerous tissues. Compared with matched invasive cancer tissues, the expression level of 14-3-3 σ in squamous metaplasia was significantly higher (P = 0.049), while that in dysplasia/carcinoma in situ showed no significant changes (P = 0.135). Statistical analysis showed that the expression level of 14-3-3 σ in tumor tissue was associated with the differentiation grade of the tumor (P = 0.001) and the prognosis of the patient (P = 0.003). The overexpression of 14-3-3 σ significantly suppressed the proliferation of H520 cells in vitro and in vivo.ConclusionThe inactivation of 14-3-3 σ may be a very early event in tumorigenesis and could facilitate the initiation and progression of lung SqCC in a sustainable way.

Knockdown of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) enhances tumorigenesis both in vivo and in vitro in bladder cancer

“…However, previous studies have reported that in some other types of cancer, 14-3-3ζ may serve as a pro-tumor molecule ( 6 , 7 , 15 , 16 ). Thus, in our first step, we verified the role of YWHAZ in three typical cancers that have been commonly reported before, breast, lung and prostate cancer.…”

“…The different binding ability may contribute to the contrasting role of different isoforms in a certain cancer type. As an instance, 14-3-3ζ promoted tumor invasion, while 14-3-3σ serves as a tumor-suppressor gene in non-small cell lung cancer ( 16 , 25 ). In addition, the expression level of 14-3-3 isoforms in tissue may be different ( 26 ).…”

Identification of microRNA differentially expressed in three subtypes of non-small cell lung cancer and in silico functional analysis

“…Recent studies suggested that TJP1 might be a useful prognostic predictor of NSCLC [ 48 , 49 ]. YWHAE , a gene encoding 14-3-3 protein, was found to involve in carcinogenesis and progression of SCC [ 50 ]. Taken together, both our findings and previous reports suggested the critical roles of three miRNAs (miR-203, miR-205 and miR-375) in regulating Hippo signaling pathway.…”

Downregulation of 14-3-3β inhibits proliferation and migration in osteosarcoma cells

“…Loss of 14-3-3σ expression has been observed in several types of human cancers, including lung cancer, breast cancer and prostate cancer (12). Expression of 14-3-3σ is significantly downregulated in cancerous lung tissues and is associated with the differentiation grade and prognosis of the patient, whereas increased 14-3-3σ expression significantly suppresses the proliferation of lung squamous cell carcinoma cells (13). 14-3-3γ is frequently upregulated in lung cancer, accompanied by loss of functional p53, which suggests that the oncogenic activities of 14-3-3γ act synergistically with the loss of p53 to promote lung tumorigenesis (14).…”