STAT3 is involved in esophageal carcinogenesis through regulation of Oct-1
Open accessAbstract
The transcription factor signal transducer and activator of transcription 3 (STAT3) contributes to cell proliferation, apoptosis and motility in human cancer cells. We aim to elucidate the function of STAT3 in esophageal carcinogenesis process and molecular mechanisms. We showed that hyperactivated STAT3 in esophageal carcinogenesis tissues correlated with the overexpression of octamer transcription factor-1 (Oct-1). High STAT3 phosphorylation correlated with shorter survival compared with low STAT3 phosphorylation. STAT3 and Oct-1 expression levels affected the proliferation and colony formation of Eca-109 esophageal squamous cell carcinoma cells by altering Erk and Akt activation. Nevertheless, STAT3 regulated the migration and invasion of esophageal squamous cell carcinoma cells independent of Oct-1. In conjunction with Oct-1, STAT3 inhibited apoptosis in esophageal squamous cell carcinoma cells. Constitutively activated STAT3 in normal human esophageal epithelium cells (HET-1A) elevated Oct-1 expression,and promoted proliferation and decreased apoptosis. STAT3 activated HET-1A cells to form tumors in vivo, suggesting that overactivated STAT3 is sufficient for carcinogenesis. We further confirmed the colocalization of STAT3 and Oct-1 in the nucleus and found that STAT3 regulates the transcription and expression of Oct-1 by directly targeting its promoter. Activated STAT3 also upregulated many genes associated with Oct-1. Together, our results indicate that STAT3 plays a crucial role in esophageal carcinogenesis by regulating the cell proliferation and apoptosis in conjunction with Oct-1.
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Activation of STAT3 is associated with emergent resistance to targeted therapies and decreased patient survival.
“In addition, activation of STAT3 is associated with emergent resistance to targeted therapies and decreased patient survival.39,40”
From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [39]
The section “STAT3 is hyperactivated in ESCC tissue with overexpression of Oct-1” (page not provided) reports shorter survival among patients whose tumors had high STAT3 phosphorylation. It does not report emergent resistance to targeted therapies; searches for targeted-therapy and drug resistance found no supporting passage. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSTAT3 target genes MMP-2 and MMP-9 are upregulated in esophageal squamous carcinoma cells (Eca-109) that express high pSTAT3, and STAT3 knockdown leads to downregulation of MMP-2 and MMP-9, dysregulation of cell migration directionality, decreased migration speed, and disorganization of F-actin formation.
“The STAT3 target genes MMP-2 and MMP-9 are upregulated in esophageal squamous carcinoma cells (Eca-109) that express high pSTAT3, and STAT3 knockdown by RNA interference in these cells leads to downregulation of MMP-2 and MMP-9, dysregulation of cell migration directionality, decreased migration speed, and disorganization of F-actin formation; this demonstrates a central role for STAT3 in MMP-2/9–”
From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [39]
In esophageal squamous carcinoma cells (Eca-109), activation of STAT3 by IL-6 treatment suppresses apoptosis, and knockdown of either STAT3 or Oct-1 enhances apoptosis.
“In these cells, activation of STAT3 by IL-6 treatment suppresses apoptosis as assessed by TUNEL staining, and knockdown of either STAT3 or Oct-1 by RNA interference enhances apoptosis.39”
From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [39]
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Bowman, T., Garcia, R., Turkson, J., & Jove, R. (2000) · Oncogene · doi:10.1038/sj.onc.1203527 · Cited by 1,743 · see citing works
Activation of STAT3 is a marker of poor prognosis in human colorectal cancer
Kusaba, T., Nakayama, T., Yamazumi, K., Yakata, Y., Yoshizaki, A., Inoue, K., Nagayasu, T., & Sekine, I. (2006) · Oncology Reports · doi:10.3892/or.15.6.1445 · Cited by 238 · see citing works
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Research works printed but not linked: 3
- Couto,J.P. et al. (2012) STAT3 negatively regulates thyroid tumorigenesis. Proc. Natl. Acad. Sci. U.S.A., 109, E2361-E2370.
- Angus,SP. et al. (2012) A role for Mediator complex subunit MED13L in Rb/E2F-induced growth arrest. Oncogene, 31(44): 4709-4717.
- Liao,YC. et al. (2011) Overexpressed hPTTG1 promotes breast can- cer cell invasion and metastasis by regulating GEF-H1/RhoA signalling. Oncogene, 31(25): 3086-3097.
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Critical analysis of the potential for targeting STAT3 in human malignancy
Grandis, J., & Peyser (2013) · OncoTargets and Therapy · doi:10.2147/ott.s47903 · Cited by 24 · see citing works
“In addition, activation of STAT3 is associated with emergent resistance to targeted therapies and decreased patient survival.(39,40) Among the first observations that indicated the importance of STAT3 in cancer was the phosphorylation of STAT3 by v-Src – a known oncoprotein at that time – as well as”
Influential
- Authors
- Wang, Z., Zhu, S., Shen, M., Liu, J., Wang, M., Li, C., Wang, Y., Deng, A., & Mei, Q.
- Affiliations
- Air Force Medical University (CN)
- Tang Du Hospital (CN)
- Xijing Hospital (CN)
- Second Military Medical University (CN)
- Corresponding author
- Mei, Qibing
- ORCID
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-11-21
- Volume
- 34
- Issue
- 3
- Pages
- 678-688
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- OpenAlex
- W2098387743
- Cited by
- 51
- References
- 2
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 6 · 2016: 1 · 2015: 9 · 2014: 11 · 2013: 5
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Carcinogenesis (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81273282, 81202353, 81001088, 30972730)
- Fourth Military Medical University
- Changhai Hospital of Shanghai (CH125530300)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- STAT3, Oct-1, esophageal squamous cell carcinoma, esophageal carcinogenesis, STAT3 phosphorylation, cell proliferation, apoptosis, cell migration and invasion, ERK activation, Akt activation, promoter regulation, esophageal epithelium
- MeSH terms
- Animals, Carcinoma, Squamous Cell, Cell Movement, Cell Survival, Cell Transformation, Neoplastic, Esophageal Neoplasms, Humans, Male, Mice, Inbred BALB C, Mice, Nude, Middle Aged, Neoplasm Transplantation, Promoter Regions, Genetic, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Apoptosis, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Organic Cation Transporter 1, Cell Line, Tumor, Tumor Burden, Cell Proliferation, STAT3 Transcription Factor, Mice
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