TWIST expression in hypopharyngeal cancer and the mechanism of TWIST-induced promotion of metastasis

Abstract

Abstract. The transcription factor TWIST is an important factor in regulating epithelial-mesenchymal transition (EMT) and tumor metastasis. To explore the functions of TWIST in hypopharyngeal cancer, we investigated if overexpression of TWIST has an effect on FaDu cell morphology, and if alteration of TWIST has an effect on E-cadherin, N-cadherin, c-fos, MMP-9, as well as in cell migration, and the invasion ability of FaDu cells. Moreover, we also studied the relationship between TWIST overexpression and clinicopathological characteristics in hypopharyngeal cancer tissue samples by immunohistochemical assays. The results showed that overexpression of TWIST-induced morphological changes, such as occurrence of EMT. TWIST overexpression also increased cell migration and invasion ability, accompanied by an alteration of E-cadherin, N-cadherin, c-fos and MMP-9 expression. Furthermore, immunohistochemical assays showed that TWIST overexpression was related with tumor differentiation (P=0.038), tumor size (P=0.048) and lymph node metastasis (P=0.044). The data presented reveal that overexpression of TWIST plays a significant role in the metastasis of hypopharyngeal tumors, and alteration of TWIST has an effect on the EMT, c-fos and MMP-9 expression in FaDu cells. We conclude that TWIST promotes hypopharyngeal carcinoma metastasis, and the TWIST/c-fos/MMP-9 signaling pathway may play an important role in the metastasis of FaDu cells. IntroductionHypopharyngeal cancer is one of the most common head and neck malignancies. More than 75% of patients with hypopharyngeal cancer are at an advanced stage at the time of diagnosis (1). Lymph node metastasis is present in 60-80% of patients and it directly affects the prognosis of the disease (2). Although the locoregional control of this cancer has been significantly improved in the last decades because of the advent of new surgical techniques and approaches, this improvement does not significantly influence the overall survival rate, partly because of metastasis (3). Therefore, understanding the potential mechanism of hypopharyngeal cancer metastasis and investigating the related targeted factors of metastasis are of primary concern.Recently, some studies have shown that TWIST, a basic helix-loop-helix (bHLH) transcription factor, is known to be essential for proper gastrulation, mesoderm formation, and neural crest migration (4). Interestingly, TWIST is required for epithelial-mesenchymal transition (EMT) (5). In addition, elevated TWIST expression was further related with tumor invasion and metastasis in esophageal squamous cell carcinomas (6). The role of TWIST in promoting EMT processes has also been reported in other solid cancers, such as prostate and uterine cancer (7,8). EMT and its accompanying reduction in E-cad expression have been shown to be essential for the extravasation of cancer cells into secondary organs (9). Previous research has confirmed that TWIST overexpression not only promotes the migration and invasion of cancers cells, but also decreases the sensitivi...

Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer

“…FOS and MYC , the well-known molecules involved in cell proliferation and differentiation were prime among them. The FOS family of genes is known to be correlated with increased aggressiveness of the tumors, their metastatic nature and thereby conferring poor prognosis in HNSCC [ 25 , 57 , 58 ]; a similar correlation was obtained from this study. MYC along with its co-amplified partner, CDK1 are reported to be correlated with survival and prognosis in head and neck cancers [ 59 – 61 ].…”

Expression and correlation of Twist and gelatinases in breast cancer

“…Lee et al (24) identified that EMT is induced by transforming growth factor (TGF)-β and Twist in mammary epithelial cells via a MMP-dependent mechanism. Yu et al (25) explored the functions of Twist in hypopharyngeal cancer tissue samples by IHC assays and the results indicated that alteration of Twist has an effect on EMT, c-fos and MMP-9 expression. Luo et al (26) transfected the Twist gene into human gastric carcinoma MKN28 cells with a Twist sense plasmid.…”

TWIST and ovarian cancer stem cells: implications for chemoresistance and metastasis

“…A growing number of studies have reported that TWIST1 is overexpressed in a variety of cancers, including breast cancer [ 48 ], gastric cancer [ 49 , 50 ], colorectal carcinoma [ 15 , 51 ], hepatocellular carcinoma [ 52 , 53 ], prostate cancer [ 54 , 55 ], bladder cancer [ 56 , 57 ], nasopharyngeal carcinoma [ 58 ], head and neck squamous cell carcinoma [ 59 , 60 ], esophageal cancer [ 61 ], endometrial cancer [ 62 ], and ovarian cancer [ 35 , 41 , 63 , 64 ]. TWIST1's role in tumor formation and progression is an active area of research and its important role is becoming increasingly evident.…”

“…Horikawa T et al suggested that the induction of TWIST1 directly contributes to the metastatic nature of nasopharyngeal carcinoma [ 59 ]. Yu L et al (2012) revealed that the overexpression of TWIST1 plays an important role in the metastasis of hypopharyngeal tumors [ 60 ]. Since TWIST1 correlated with EMT and c-fos and MMP-9 expression, they concluded that the TWIST/c-fos/MMP-9 pathway might play an important role in the metastasis of cells.…”