SEMA3B improves the survival of patients with esophageal squamous cell carcinoma by upregulating p53 and p21

Abstract

As one of the most common malignancies, esophageal squamous cell carcinoma (ESCC) is ranked as the sixth leading cause of cancer-related death worldwide. In our previous study, by employing cDNA microarray analysis, semaphorin 3B (SEMA3B) was found to be significantly downregulated in ESCC. In the present study, SEMA3B downregulation at the mRNA level was found in 34 of 60 primary ESCCs (56.7%) and in 6 of 9 ESCC cell lines (66.7%) by transcription-polymerase chain reaction (RT-PCR). Moreover, immunohistochemical (IHC) staining of SEMA3B in a tissue microarray further indicated that downregulated expression of SEMA3B protein was found in 125 of 222 (56.3%) ESCC cases and downregulation of SEMA3B protein was significantly correlated with lymph node metastasis (P=0.000), advanced clinicopathological stage (P=0.001) and poor disease-specific survival (P=0.017) of ESCC patients. In addition, functional studies demonstrated that the SEMA3B gene could suppress the tumorigenic ability of ESCC cells and cell motility. Furthermore, it was found that by upregulating p53 and p21 expression and inhibiting Akt (Ser473) phosphorylation, SEMA3B could induce cell cycle arrest at G1/S phase. Taken together, our results suggest that SEMA3B may be an important tumor-suppressor gene in the malignant progression of ESCC, as well as a valuable prognostic marker for ESCC patients.

Polymorphism rs2395655 affects LEDGF/p75 binding activity and p21WAF1/CIP1 gene expression in esophageal squamous cell carcinoma

“…Our results were consistent with those reports implying the positive prognostic role of elevated p21 expression in ESCC. 7,8,[10][11][12][13] However, several other reports suggested an adverse prognostic role of up-regulated p21 expression for ESCC patients. 5,6,9 The inconsistency among these studies is most likely due to inadequate study design, limited populations with different geographic locations, or even different esophageal cancer types.…”

Phosphorylation-Dependent Inhibition of Akt1

“…In close agreement with our findings, studies in adipocytes found that half-maximal Akt1 cellular signaling activity is achieved when the kinase is 5–22% phosphorylated [ 13 ]. In studies of human tumors [ 12 , 13 , 14 , 15 ] and in clinical diagnostic settings [ 14 , 15 ], the phosphorylation status of Akt1 at Ser473 only is often used as a marker or proxy for Akt1 activity. Our work [ 12 ] and work by others [ 16 ] found that phosphorylation of Thr308 alone was sufficient for maximal Akt1 signal prorogation in cells.…”

Epidermal growth factor‐containing fibulin‐like extracellular matrix protein 1 (EFEMP1) suppressed the growth of hepatocellular carcinoma cells by promoting Semaphorin 3B(SEMA3B)

“…Among the members of these signaling pathways, we noticed the SEMA3B gene. First, the microarray results suggested that SEMA3B was significantly altered in the chip, and it is included in the Axon guidance pathway and the Neuroscience pathway found by pathway analysis . Moreover, the SEMA3B gene was thought to play an important role in regulating cellular senescence and apoptosis .…”