TWIST1 activates cancer stem cell marker genes to promote epithelial-mesenchymal transition and tumorigenesis in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers worldwide. Overexpression of EMT master transcription factors can promote differentiated cells to undergo cancer reprogramming processes and acquire a stem cell-like status. METHODS: The KYSE-30 and YM-1 ESCC cell lines were transduced with retroviruses expressing TWIST1 or GFP and analyzed by quantitative reverse transcription PCR (qRT-PCR), chromatin immunoprecipitation (ChIP), and immunostaining to investigate the correlation between TWIST1 and stemness markers expression. Cells expressing TWIST1 were characterized for mRNA candidates by qRT-PCR and for protein candidates by Flow cytometry and Immunocytochemistry. TWIST1-ESCC cells were also evaluated for apoptosis and drug resistance. RESULTS: Here we identify a role for TWIST1 in the establishment of ESCC cancer stem cell (CSC)-like phenotype, facilitating the transformation of non-CSCs to CSCs. We provide evidence that TWIST1 expression correlates with the expression of CSC markers in ESCC cell lines. ChIP assay results demonstrated that TWIST1 regulates CSC markers, including CD44, SALL4, NANOG, MEIS1, GDF3, and SOX2, through binding to the E-box sequences in their promoters. TWIST1 promoted EMT through E-cadherin downregulation and vimentin upregulation. Moreover, TWIST1 expression repressed apoptosis in ESCC cells through upregulation of Bcl-2 and downregulation of the Bax protein, and increased ABCG2 and ABCC4 transporters expression, which may lead to drug resistance. CONCLUSIONS: These findings support a critical role for TWIST1 in CSC-like generation, EMT progression, and inhibition of apoptosis in ESCC. Thus, TWIST1 represents a therapeutic target for the suppression of esophageal cell transformation to CSCs and ESCC malignancy.

PYGO2 as an independent diagnostic marker expressed in a majority of colorectal cancers.

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers worldwide. Detection of CRC at the early stages of disease can play an important role in decrease of associated mortality rates. The Wnt signaling pathway is crucial for the progression of different cellular and developmental processes and Wnt pathway deregulation has been well characterized in a variety of cancers, particularly in CRC. The aim of this study was to analyze protein expression of Pygopus2 (PYGO2), the main transcription factor of Wnt pathway, in CRC tissues and evaluate its probable correlation with clinicopathological features of the patients. The expression pattern of PYGO2 was evaluated by immunohistochemistry in tumor tissues and their margin normal which is the piece of normal, or unaffected tissue excised from the surrounding the visible tumors in 46 CRC patients. A defined scoring system was applied to analyze immunostaining results. The expression of PYGO2 protein was detected in all tumor tissues. Furthermore, this expression was significantly higher in CRC samples than in normal tissues. There was a significant association between PYGO2 protein expression in CRC and tumor cell metastasis to the lymph nodes. Considering the significant expression of PYGO2 protein in colorectal tumor cells and its correlation with lymph node metastasis, this protein may be used as a biomarker for metastatic CRC as well as a putative therapeutic target to inhibit aggressiveness and metastasis of CRC.

Hormone receptor expression and clinicopathologic features in male and female breast cancer.

BACKGROUND: Male and female breast cancers were investigated for variation in the clinicopathologic characteristics and expression of steroid hormone receptors in the northeast of Iran. MATERIALS AND METHODS: Tumor specimens of 17 males and 338 females with breast cancer were collected at the hospitals of Mashhad University of Medical Sciences. Immunohistochemical expression of hormone receptors and clinicopathologic features of breast cancer were compared between two groups. RESULTS: The mean age in men was 15 years higher than women (p=0.000). Males and females were mainly in stage II and III respectively (p=0.007). Although more than 60% of male and female patients were grade II, the respective figures for grade I and III were 25% and 12.5% in men but 7.1% and 27.2% in women respectively (p=0.025). ER was significantly more positive in men against women; 82.3% versus 53.4% (p=0.016). The related measures for PR was 58.8% and 50.3%, respectively (p=0.424). Males also showed significantly more ER expression than postmenopausal females; 82.3% versus 48.9% (p=0.010). CONCLUSIONS: Breast cancer in males and females contrasted in age at diagnosis, histological type, stage, grade and ER expression which emphasize they are separate diseases with different behaviors.