SOX2 inhibits metastasis in gastric cancer

Chen, Yansu; Huang, Yefei; Zhu, Liwen; Chen, Minjuan; Huang, Yulin; Zhang, Jianbing; He, Song; Li, Aiping; Chen, Rui; Zhou, Jianwei

doi:10.1007/s00432-016-2125-4

Cited by 35 publications

(35 citation statements)

References 47 publications

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“…These data indicated the stimulation of lymphatic metastasis in HNSCC patients by low expression levels of SOX2 . Comparable results have been published by other groups for both gastric cancer patients [44] and HNSCC patients [41, 42] in terms of a significant correlation between high SOX2 expression levels and a negative lymph node status. However, our functional analyses on UM-SCC1 cells did not support this hypothesis; by contrast, we showed stimulation of cell migration when the SOX2 gene was overexpressed by plasmid transfection (Figure 5).…”

Section: Discussionsupporting

confidence: 80%

“…3q26 amplification represents a highly frequent chromosomal alteration in HNSCCs [11, 12] and encodes the genes SEC62 and SOX2 , which have both been shown to be overexpressed in various cancers [13–15, 45], including HNSCCs [27, 35, 46], and to affect the metastatic potential of cancer cells [22, 23, 26, 37, 39–42, 44, 47]. Moreover, the expression levels of both genes in tumor tissue showed prognostic relevance in HNSCC patients [37, 35, 42, 48, 49].…”

Section: Discussionmentioning

confidence: 99%

“…Compared with SEC62 , SOX2 also seems to affect the migration and metastasis of cancer cells; an analysis of SOX2 expression in HNSCC tissue specimens showed a significant correlation with positive lymph node status, [38] and artificial SOX2 overexpression in laryngeal cancer cells stimulated their migratory potential [39, 40]. By contrast, other studies have shown a correlation between high SOX2 expression and negative lymph node status in HNSCC patients [41, 42], as well as a favorable prognosis in NSCLC [43], gastric cancer [44] and HNSCC patients [42]. Ultimately, the role of SOX2 in cancer cell biology and the formation of metastases remain unclear and require further studies.…”

Section: Introductionmentioning

confidence: 99%

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Effect of 3q oncogenes SEC62 and SOX2 on lymphatic metastasis and clinical outcome of head and neck squamous cell carcinomas

et al. 2016

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Chromosome 3q26 amplification represents a frequent alteration in head and neck squamous cell carcinomas (HNSCCs). Overexpression of 3q26 encoded genes SEC62 and SOX2 was detected in various cancers, including HNSCCs, indicating their potential function as oncogenes. In our study, we elucidated the function of SEC62 and SOX2 in HNSCC patients, with a main focus on their effect on lymphatic metastasis and patient survival. We analyzed SEC62 and SOX2 expression in tissue specimens from 65 HNSCC patients and 29 patients with cervical cancer of unknown primary (CUP); a higher SEC62 and lower SOX2 expression was observed in the lymph node metastases from HNSCC patients compared with the respective primary tumor. Lymph node metastases from CUP patients showed higher SEC62 and lower SOX2 expression compared with lymph node metastases from HNSCC patients. When proceeding from the N1 to the N3 stage, SEC62 expression in the lymph node metastases showed an increase and SOX2 expression showed a decrease. Moreover, both genes showed a highly significant relevance as prognostic biomarkers, with the worst prognosis for patients with high SEC62 and low SOX2 expression levels. In functional analyses, knockdown of SEC62 resulted in an inhibition of HNSCC cell migration while, conversely, SEC62 and SOX2 overexpression stimulated cell migration. Taken together, our study showed that the expression of the 3q oncogenes SEC62 and SOX2 affects lymphatic metastasis and cell migration in HNSCC and CUP patients and has a high prognostic relevance in these diseases.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of 3q oncogenes SEC62 and SOX2 on lymphatic metastasis and clinical outcome of head and neck squamous cell carcinomas

et al. 2016

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“…In addition to inhibiting CDK activity, P21 binds to proliferating cell nuclear antigen (PCNA) and prevents it from activation of DNA polymerase, an activity required for DNA replication and repair. It plays an important role in regulating the proliferation, apoptosis, differentiation [5–7], metastasis [8] and stemness of cancer cells [9]. The losses of both expression and topological regulation of p21 is commonly detected in colorectal cancer [10].…”

Section: Introductionmentioning

confidence: 99%

Specific up-regulation of p21 by a small active RNA sequence suppresses human colorectal cancer growth

et al. 2017

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The double stranded small active RNA (saRNA)- p21-saRNA-322 inhibits tumor growth by stimulating the p21 gene expression. We focused our research of p21-saRNA-322 on colorectal cancer because 1) p21 down-regulation is a signature abnormality of the cancer, and 2) colorectal cancer might be a suitable target for in situ p21-saRNA-322 delivery. The goal of the present study is to learn the activity of p21-saRNA-322 in colorectal cancer. Three human colorectal cancer cell lines, HCT-116, HCT-116 (p53–/−) and HT-29 were transfected with the p21-saRNA-322. The expression of P21 protein and p21 mRNA were measured using the Western blot and reverse transcriptase polymerase chain reaction (RT-PCR). The effect of p21-saRNA-322 on cancer cells was evaluated in vitro; and furthermore, a xenograft colorectal tumor mode in mice was established to estimate the tumor suppressing ability of p21-saRNA-322 in vivo. The results showed that in all three colorectal cancer cell lines, the expression of p21 mRNA and P21 protein were dramatically elevated after p21-saRNA-322 transfection. Transfection of p21-saRNA-322 caused apoptosis and cell cycle arrest at the G0/G1. Furthermore, anti-proliferation effect, reduction of colonies formation and cell senescence were observed in p21-saRNA-322 treated cells. Animal studies showed that p21-saRNA-322 treatment significantly inhibited the HT-29 tumor growth and facilitated p21 activation in vivo. These results indicated that, p21-saRNA-322-induceded up-regulation of p21 might be a promising therapeutic option for the treatment of colorectal cancer.

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“…Sox2 was reported as a tumor suppressor that inhibits cell growth by either regulating cyclin D1, phosphorylated Rb, or p27 (Kip1) levels[39], or directly activating PTEN[13]. In addition, Sox2 has been shown to inhibit migration and invasion by upregulating p21 expression in gastric cancer[40]. However, others demonstrated that Sox2 operates as an oncogene in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Predictive Value of Stemness Factor Sox2 in Gastric Cancer Is Associated with Tumor Location and Stage

Yang

Kang

et al. 2017

PLoS ONE

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Cancer stem cells (CSCs) are thought to be the "root" of cancer. Although stemness-related factors ALDH1A1 and Sox2 have been used as markers to identify gastric CSCs, the expression pattern and significance of these factors in gastric cancer have not been sufficiently demonstrated. In this study, the expressions of ALDH1A1 and Sox2 were detected by immunohistochemistry in 122 gastric cancer specimens. And the correlation between Sox2 or ALDH1A1 expression and clinicopathological parameters and overall survival data were analyzed. The positive rate of ALDH1A1 expression was 60%, but there was no significant difference between survival rates of ALDH1A1-positive and ALDH1A1-negative patients. Sox2 was expressed in 42% of specimens and was associated with poor prognosis of patients (P = 0.015). Stratified analysis showed that Sox2 expression correlated with shorter lifespan only in patients with cardiac gastric cancers (P = 0.002) or stage I or II gastric cancers (P = 0.002); but not in patients with non-cardiac cancers (P = 0.556) or stage III or IV gastric cancers (P = 0.121). Analysis on a database cohort validated the correlation between Sox2 expression and poor prognosis in stage II cancer. Also, expression of Sox2 was associated with lymphnode metastasis in patients with cardiac gastric cancer (P = 0.037). A multivariate analysis revealed that Sox2 was an independent prognostic factor in cardiac gastric cancer. Our results indicate that predictive value of Sox2 in gastric cancer is associated with cardiac cancer location and with early cancer stages (I and II).

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SOX2 inhibits metastasis in gastric cancer

Cited by 35 publications

References 47 publications

Effect of 3q oncogenes SEC62 and SOX2 on lymphatic metastasis and clinical outcome of head and neck squamous cell carcinomas

Effect of 3q oncogenes SEC62 and SOX2 on lymphatic metastasis and clinical outcome of head and neck squamous cell carcinomas

Specific up-regulation of p21 by a small active RNA sequence suppresses human colorectal cancer growth

Predictive Value of Stemness Factor Sox2 in Gastric Cancer Is Associated with Tumor Location and Stage

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