The dark and the bright side of Stat3: proto-oncogene and tumor-suppressor.

@article{Ecker2009TheDA,
  title={The dark and the bright side of Stat3: proto-oncogene and tumor-suppressor.},
  author={Andrea Ecker and Olivia Simma and Andrea Hoelbl and Lukas Kenner and Hartmut Beug and Richard Moriggl and Veronika Sexl},
  journal={Frontiers in bioscience},
  year={2009},
  volume={14},
  pages={
          2944-58
        }
}
Stat transcription factors have been implicated in tumorigenesis in mice and men. Stat3 and Stat5 are considered powerful proto-oncogenes, whereas Stat1 has been demonstrated to suppress tumor formation. We demonstrate here for the first time that a constitutive active version of Stat3alpha (Stat3alphaC) may also suppress transformation. Mouse embryonic fibroblasts (MEFs) deficient for p53 can be transformed with either c-myc or with rasV12 alone. Interestingly, transformation by c-myc is… 
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Loss of STAT3 in Lymphoma Relaxes NK Cell-Mediated Tumor Surveillance

Investigating the effects of STAT3 deletion in a BCR/ABL-induced lymphoma model indicates that STAT3 inhibition in lymphoma patients will impair NK cell-mediated tumor surveillance, which needs to be taken into account when testing STAT3 inhibitors in preclinical or clinical trials.

STAT3 suppresses transcription of proapoptotic genes in cancer cells with the involvement of its N-terminal domain

A suppressive role for theSTAT3 ND in the regulation of proapoptotic gene expression in cancer cells is demonstrated, providing further support for targeting STAT3 ND for cancer therapy.

Disruption of STAT3 signalling promotes KRAS-induced lung tumorigenesis

It is demonstrated that STAT3 plays an unexpected tumour-suppressive role in KRAS mutant lung adenocarcinoma (AC) by sequestering NF-κB within the cytoplasm, thereby inhibiting IL-8-mediated myeloid tumour infiltration and tumour vascularization and hence tumour progression.

STAT3 in Cancer—Friend or Foe?

The roles of STAT3 in cancer are multi-faceted and far more complicated than one appreciated previously, and several possible mechanisms linked to the role ofSTAT3β, one of the two STAT3 splicing isoforms are discussed.

Loss of STAT3 in murine NK cells enhances NK cell-dependent tumor surveillance.

Investigating the function of STAT3 in NK cells with Stat3(Δ/Δ)Ncr1-iCreTg mice suggests that STAT3 inhibitors will stimulate the cytolytic activity of NK cells against leukemia, thereby providing an additional therapeutic benefit.

Stat3 is required for anchorage‐independent growth and metastasis but not for mammary tumor development downstream of the ErbB‐2 oncogene

The data suggest that Stat3 might be a useful therapeutic target in breast tumors showing amplification and/or overexpression of the ErbB‐2 oncogene, which normally display aggressive, metastatic behavior.

STAT3β controls inflammatory responses and early tumor onset in skin and colon experimental cancer models.

The results suggest that STAT3β, by limiting inflammation during the initial phases of tumorigenesis, contributes to tissue homeostasis and counteracts malignant transformation and initial tumor growth.

The Opposing Function of STAT3 as an Oncoprotein and Tumor Suppressor Is Dictated by the Expression Status of STAT3β in Esophageal Squamous Cell Carcinoma

STAT3β suppresses chemoresistance and cancer stemness by blocking the transcriptional activity of STAT3α, one of the two STAT3 isoforms, and is an independent protective prognostic marker in patients with ESCC.

p19ARF/p14ARF controls oncogenic functions of signal transducer and activator of transcription 3 in hepatocellular carcinoma

Signal transducer and activator of transcription 3 (Stat3) is activated in a variety of malignancies, including hepatocellular carcinoma (HCC), and evidence is shown that p19ARF/p14ARF determines the pro‐ or anti‐oncogenic activity of U‐Stat3 and pY‐stat3 in Ras‐dependent HCC progression.

Targeting Signal Transducers and Activators of Transcription-3 (Stat3) As a Novel Strategy In Sensitizing Breast Cancer To Egfr-Targeted Therapy

  • H. Lo
  • Biology, Medicine
  • 2008
Findings to date point to significant in vivo and in vitro interactions between EGFR and STAT3 oncoproteins in breast cancer as well as a role of STAT3 constitutive activation may play in the resistance of these tumors to anti-EGFR therapy.
...

References

SHOWING 1-10 OF 60 REFERENCES

New and Old Functions of STAT3: A Pivitol Target for Individualized Treatment of Cancer

Genetic tools to evaluate STAT-dependent malignancy are developed and it is shown that survival and growth of lymphoid malignancies requires expression of STAT3 and STAT3-null fibroblasts are resistant to transformation by a variety of oncogenes.

STAT1 acts as a tumor promoter for leukemia development.

Constitutively Activated Stat3 Induces Tumorigenesis and Enhances Cell Motility of Prostate Epithelial Cells through Integrin β6

The sufficiency of constitutively activated Stat3 in mediating prostate tumorigenesis is demonstrated and novel Stat3 targets that are involved in promoting cell migration and transformation are identified.

Disruption of Stat3 reveals a critical role in both the initiation and the promotion stages of epithelial carcinogenesis.

These data provide the first evidence that Stat3 is required for de novo epithelial carcinogenesis, through maintaining the survival of DNA-damaged stem cells and through mediating and maintaining the proliferation necessary for clonal expansion of initiated cells during tumor promotion.

Stat3 as an Oncogene

Overexpression of a dominant negative form of STAT3 selectively impairs hematopoietic stem cell activity

HSCs express non-limiting levels of STAT3 which, nevertheless, play an important stage-specific and non-redundant role in maintaining the function of HSCs stimulated to divide in adult marrow tissue.

Loss of SOCS3 Gene Expression Converts STAT3 Function from Anti-apoptotic to Pro-apoptotic*

The data suggest that prolonged activation of STAT3 could induce apoptosis/growth arrest rather than anti-apoptosis and proliferation in certain cases, and SOCS3 is a critical regulator of this balance.

JunB is a gatekeeper for B-lymphoid leukemia

It is found that JunB functions as a gatekeeper during tumor evolution, in its absence, transformed leukemic cells acquire an enhanced proliferative capacity, which presages a more malignant disease.

Stat3 is required for ALK-mediated lymphomagenesis and provides a possible therapeutic target

It is shown by gene targeting that Stat3 is required for the transformation of mouse embryonic fibroblasts in vitro, for the development of B-cell lymphoma in transgenic mice and for the growth and survival of both human and mouse NPM-ALK–transformed B and T cells.

Role of Stat3 in Regulating p53 Expression and Function

ABSTRACT Loss of p53 function by mutation is common in cancer. However, most natural p53 mutations occur at a late stage in tumor development, and many clinically detectable cancers have reduced p53…
...