Upregulation and inhibition of the nuclear translocation of Oct4 during multistep gastric carcinogenesis

Al-Marzoqee, Fathyia Y; Khoder, Ghalia; Al-Awadhi, Haifa; John, Rony; Beg, Azam; Vincze, Áron; Branicki, Frank J.; Karam, Sherif M.

doi:10.3892/ijo.2012.1608

Cited by 29 publications

(22 citation statements)

References 38 publications

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“…It was revealed that the expression of OCT4 was elevated in the nucleus of cancer tissue cells and was associated with tumor differentiation; however, OCT4 did not correlate with tumor size and lymph node metastases. The present study, coupled with other studies, may indicate a possible association between OCT4 nuclear accumulation and turmorigenesis (23). OCT4 was also differentially expressed in pancreatic cancer cells with different degrees of differentiation, of which the Panc-1 cell line had the highest expression level of OCT4.…”

Section: Discussionsupporting

confidence: 84%

Knockdown of OCT4 suppresses the growth and invasion of pancreatic cancer cells through inhibition of the AKT pathway

Lin

Sun

Han

et al. 2014

Molecular Medicine Reports

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Octamer-binding transcription factor 4 (OCT4) is one of the factors associated with self-renewal and differentiation in cancer stem cells, and is crucial for the progression of various types of human malignancy. However, the expression and function of OCT4 in human pancreatic cancer has not been fully elucidated. The purpose of the present study was to investigate the function and molecular mechanisms of OCT4 in pancreatic cancer cells. The clinical significance of OCT4 expression was assessed by an immunohistochemical assay using a tissue microarray procedure in pancreatic cancer tissues and cells with different degrees of differentiation. A loss-of-function approach was used to examine the effects of a lentivirus-mediated OCT4 small hairpin RNA vector on biological behaviors, including cell proliferative activity and invasive potential. The results demonstrated that the expression levels of OCT4 protein in cancer tissues were significantly elevated compared with those in adjacent non-cancerous tissues (65.0 vs. 42.5%; P=0.005), which was correlated with tumor differentiation (P=0.008). The knockdown of OCT4 inhibited the proliferation and invasion of pancreatic cancer cells (Panc-1) expressing high levels of OCT4, accompanied with decreased expression of AKT, proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2 (MMP-2). In conclusion, the present study reveals that the increased expression of OCT4 is correlated with the differentiation of pancreatic cancer, while knockdown of OCT4 suppresses the growth and invasion of pancreatic cancer cells through inhibition of AKT pathway-mediated PCNA and MMP-2 expression, suggesting that OCT4 might serve as a potential therapeutic target for the treatment of pancreatic cancer.

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Section: Discussionsupporting

confidence: 84%

Knockdown of OCT4 suppresses the growth and invasion of pancreatic cancer cells through inhibition of the AKT pathway

Lin

Sun

Han

et al. 2014

Molecular Medicine Reports

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“…These pluripotency-inducing factors have been detected in embryonic stem cells, as well as in normal cells and cancer cells, including gastric cancer (9). Although these factors are necessary in order for stem cells to acquire pluripotency, it has been suggested that they may have oncogenic potential in normal cells (10).…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of KLF4 expression in gastric cancer

et al. 2016

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Abstract.To understand the roles of pluripotent stem cell-inducing genes in gastric cancer, the expression of Krüppel-like factor 4 (KLF4), Nanog, octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc) and sex-determining region Y-box 2 (SOX2) was examined using the newly developed gastric carcinoma tissue microarray. The associations between the immunohistochemical expression levels of the pluripotency-inducing factors and the clinicopathological data of 108 patients with gastric cancer were analyzed. No associations were identified between the expression levels of the five pluripotency-inducing factors and the tumor-node-metastasis (TNM) classification or clinicopathological characteristics of the patients. In addition, multivariate analysis revealed no association of Nanog, Oct4, SOX2 or c-Myc with the prognosis of the gastric cancer patients; however, low expression of KLF4 was determined to be an independent negative prognostic factor (P=0.0331), particularly in patients who underwent R0 resection (TNM stages 2 and 3; P=0.0048). In summary, low KLF4 expression was found to be negatively associated with overall survival, and may therefore be a useful prognostic marker in gastric cancer patients. IntroductionGastric cancer is a malignant tumor with a poor prognosis, and the various treatments available at present, including surgery, chemotherapy and radiotherapy, remain unsatisfactory (1). Development of gastric cancer is associated with a number of molecular abnormalities, the majority of which affect the downstream signal transduction pathways involved in cell growth and differentiation (2,3). Investigation into such molecules is expected to provide useful prognostic biomarkers of gastric cancer that will aid in determining the treatment plan for individual patients. For example, methylation of the XIAP-associated factor 1 promoter (4), and expression of 14-3-3σ (5) and miR-200c (6) have been reported to be important for the prediction of poor prognosis in gastric cancer patients; however, further investigation is required.Induced pluripotent stem (iPS) cells are cells that have acquired pluripotency following the introduction of various factors; octamer-binding transcription factor (Oct)3/4 and sex-determining region Y-box 2 (SOX2) plus Krüppel-like factor 4 (KLF4) and avian myelocytomatosis viral oncogene homolog (c-Myc), or Nanog and LIN28 have been shown to induce pluripotency in various murine and human cells (e.g., fibroblasts) (7,8). These pluripotency-inducing factors have been detected in embryonic stem cells, as well as in normal cells and cancer cells, including gastric cancer (9). Although these factors are necessary in order for stem cells to acquire pluripotency, it has been suggested that they may have oncogenic potential in normal cells (10).Expression of SOX2 has been reported to be important for tumorigenicity and chemoresistance (11). However, the inhibition of gastric cancer cell growth and the induction of apoptosis by SOX2 has also been rep...

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“…18,19 There have been studies that reported that Oct4 is overexpressed in many kinds of cancers, such as, lung cancer, oral squamous cell carcinoma, GC, breast cancer, and esophageal cancer and ectopic expression may play a role in the improvement of disease. [20][21][22][23] Nevertheless, there is little relation between MUC5AC and Oct4 with clinical factors in GC, and contradictory findings have been reported. In addition to clinical outcome, lymph node and distant metastasis has been shown to be important factors for prognostic in GC.…”

Section: In Addition Low Expression Of Muc5ac and High Expression Ofmentioning

confidence: 99%

Differential expression of two genes Oct‐4 and MUC5AC associates with poor outcome in patients with gastric cancer

Javanbakht

Akhavan-Moghadam

Talaei

et al. 2017

Clin Exp Pharma Physio

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Gastric cancer (GC) is the most frequent leading cause of cancer-associated mortality worldwide that is linked to poor prognosis due to the lack of appropriate biomarkers. Our aim was to evaluate the MUC5AC and Oct-4 expression levels in GC and to assess their association with clinical factors. Immunohistochemical analysis (IHC) and qRT-PCR were performed in GC patients to examine the MUC5AC and Oct-4 expression levels. The mRNA level of MUC5AC was significantly decreased in tumour tissues compared with non-cancerous tissues (1.11 ± 0.69 vs 3.7 ± 0.71; P = .024). On the other hand, Oct-4 mRNA level was upregulated in tumour tissues as compared to normal tissues (2. 86 ± 0.78 vs 0.87 ± 0.54; P = .0015). Decreased expression of MUC5AC was detected in 27 patients (67.5%), while high to moderate expression levels were observed in 13 cases (32.5%), but in normal tissues the expression levels of MUC5AC were increased (P = .001). The decreased expression of MUC5AC was associated with aggressive tumour characteristics, such as TNM stage (P = .023), histologic type (P = .012) and lymph node metastasis (P = .001). High expression of Oct-4 was detected in 24 tumour tissues (60%), while 16 cases (40%) showed low expression level. Increased Oct-4 expression was correlated with clinicopathological characteristics such TNM stage (P = .002), histologic type (P = .008) and lymph node metastasis (P = .001). Our results showed that high Oct-4 expression and the reduction of MUC5AC expression may be involved in the progression and an unfavorable prognosis of GC.

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Upregulation and inhibition of the nuclear translocation of Oct4 during multistep gastric carcinogenesis

Cited by 29 publications

References 38 publications

Knockdown of OCT4 suppresses the growth and invasion of pancreatic cancer cells through inhibition of the AKT pathway

Knockdown of OCT4 suppresses the growth and invasion of pancreatic cancer cells through inhibition of the AKT pathway

Prognostic significance of KLF4 expression in gastric cancer

Differential expression of two genes Oct‐4 and MUC5AC associates with poor outcome in patients with gastric cancer

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