Role of STAT3 in Cancer Metastasis and Translational Advances

Kamran, Mohammad Zahid; Patil, Prachi; Gude, Rajiv P.

doi:10.1155/2013/421821

Cited by 335 publications

(277 citation statements)

References 139 publications

(158 reference statements)

Supporting

Mentioning

272

Contrasting

Unclassified

Order By: Relevance

“…In this study, we found that ATF3 was upregulated in skin cancer tissues from patients and that ATF3 promoted skin cancer cell proliferation through activating Stat3 phosphorylation, which is the hallmark of various cancers development (Hodge et al, 2005;Yu et al, 2009;Kamran et al, 2013). Furthermore, activation of Stat3 by ATF3 was dependent on repression of p53 expression and the induction of p53-Stat3 signaling cascade accounted for the promotion effect of ATF3 on skin cancer cell proliferation.…”

Section: Introductionmentioning

confidence: 68%

ATF3 Activates Stat3 Phosphorylation through Inhibition of p53 Expression in Skin Cancer Cells

Hao¹,

J²,

Zhang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Aim: ATF3, a member of the ATF/CREB family of transcription factors, has been found to be selectively induced by calcineurin/NFAT inhibition and to enhance keratinocyte tumor formation, although the precise role of ATF3 in human skin cancer and possible mechanisms remain unknown. Methods: In this study, clinical analysis of 30 skin cancer patients and 30 normal donors revealed that ATF3 was accumulated in skin cancer tissues. Functional assays demonstrated that ATF3 significantly promoted skin cancer cell proliferation. Results: Mechanically, ATF3 activated Stat3 phosphorylation in skin cancer cell through regulation of p53 expression. Moreover, the promotion effect of ATF3 on skin cancer cell proliferation was dependent on the p53-Stat3 signaling cascade. Conclusion: Together, the results indicate that ATF3 might promote skin cancer cell proliferation and enhance skin keratinocyte tumor development through inhibiting p53 expression and then activating Stat3 phosphorylation.

show abstract

Section: Introductionmentioning

confidence: 68%

ATF3 Activates Stat3 Phosphorylation through Inhibition of p53 Expression in Skin Cancer Cells

Hao¹,

J²,

Zhang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…The three main mechanisms by which SOCS protein can inhibit STAT3 signaling involves, i) by competing with STAT3 for binding to pTyr motif of activated receptor, ii) by directly binding to JAK receptor and inactivating it, or iii) by binding to signaling protein and targeting it for proteasomal degradation through SOCS box domain [40]. Apart from acting as inhibitor of STAT3 signaling, SOCS3 is also a downstream transcriptional target of STAT3 pathway.…”

Section: Socs3 Proteinsmentioning

confidence: 99%

“…However, under normal condition the SOCS3 signaling is under stringent control. In several cancers, the loss of SOCS3 expression due to epigenetic alteration leads to enhanced STAT3 signaling that in turn increases overall cell survival and proliferation [40,41]. In breast cancer patients, loss of SOCS3 expression was considered as a biomarker for poor prognosis and was shown to be associated with increased lymph node metastasis [42].…”

Section: Socs3 Proteinsmentioning

confidence: 99%

Approaching non-canonical STAT3 signaling to redefine cancer therapeutic strategy

Dimri¹,

Sukanya²,

De³

2017

Integr Mol Med

View full text Add to dashboard Cite

STAT3 is an essential cellular transcription factor that activates a cascade of survival and proliferation signaling program in cells upon cytokine and growth factor stimulus. STAT3 forms a converging point for many upstream activated signaling pathways required for maintaining normal and oncogenic condition. As an active transcription factor, it controls transcription of downstream genes involved in various steps of cancer progression like cell proliferation, migration, immune evasion and angiogenesis. It is known to be constitutively active in many cancers with approximately 40% of breast cancer cases positive for activated STAT3. Apart from the wellstudied pY705 activation (canonical pathway), STAT3 is reported to undergo alternative post-translational modifications like pS727 and K685Ac (non-canonical pathway) that are now appearing to be responsible for triggering activated STAT3 in many cancers including breast cancer. Hence, correct designation and targeting ability of these post-translational modifications (PTM) of STAT3 signaling in any particular cancer may hold the key in treating patients with STAT3 overexpression.

show abstract

“…Stat3 was revealed as the nodal convergence point between PR and HRG/ErbB-2 signaling in BC (Proietti et al 2005(Proietti et al , 2009). Interestingly, Stat3 plays a key role in mammary cancer (reviewed in Kamran et al 2013). Nuclear interaction between PR and ErbB-2 was next identified, showing that PR activated by its ligands (the steroid hormones progestins) induces ErbB-2 nuclear translocation and its colocalization and physical association with Stat3 in the nuclear compartment of BC cells.…”

Section: :12mentioning

confidence: 99%

“…The critical role of both Stat3 and MErbB-2 in BC metastasis has long been demonstrated (reviewed in Freudenberg et al 2009, Kamran et al 2013. Furthermore, a series of BC models where transgenic mice carry ErbB-2 under the control of the mouse mammary tumor virus (MMTV) promoter disclosed the involvement of Stat3 as a downstream effector of MErbB-2-induced metastatic dissemination in BC (Muller et al 1988, Guy et al 1992, Siegel et al 1999, Finkle et al 2004, Ursini-Siegel et al 2008.…”

Section: :12mentioning

confidence: 99%

ErbB-2 nuclear function in breast cancer growth, metastasis and resistance to therapy

Elizalde¹,

Russo²,

Chervo³

et al. 2016

Endocrine-Related Cancer

View full text Add to dashboard Cite

Approximately 15-20% of breast cancers (BC) show either membrane overexpression of ErbB-2 (MErbB-2), a member of the ErbBs family of receptor tyrosine kinases, or ERBB2 gene amplification. Until the development of MErbB-2-targeted therapies, this BC subtype, called ErbB-2-positive, was associated with increased metastatic potential and poor prognosis. Although these therapies have significantly improved overall survival and cure rates, resistance to available drugs is still a major clinical issue. In its classical mechanism, MErbB-2 activates downstream signaling cascades, which transduce its effects in BC. The fact that ErbB-2 is also present in the nucleus of BC cells was discovered over twenty years ago. Also, compelling evidence revealed a non-canonical function of nuclear ErbB-2 as a transcriptional regulator. As a deeper understanding of nuclear ErbB-2 actions would be crucial to the disclosure of its role as a biomarker and a target of therapy in BC, we will here review its function in BC, in particular, its role in growth, metastatic spreading and response to currently available MErbB-2-positive BC therapies.

show abstract

Role of STAT3 in Cancer Metastasis and Translational Advances

Cited by 335 publications

References 139 publications

ATF3 Activates Stat3 Phosphorylation through Inhibition of p53 Expression in Skin Cancer Cells

ATF3 Activates Stat3 Phosphorylation through Inhibition of p53 Expression in Skin Cancer Cells

Approaching non-canonical STAT3 signaling to redefine cancer therapeutic strategy

ErbB-2 nuclear function in breast cancer growth, metastasis and resistance to therapy

Contact Info

Product

Resources

About