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    Correction: The pleiotropic effects of TNF? in breast cancer subtypes is regulated by TNFAIP3/A20 (Oncogene, (2019), 38, 4, (469-482), 10.1038/s41388-018-0472-0)
    (Nature Publishing Group, 2019) Lee, Eunmi; Ouzounova, Maria D.; Piranlıoğlu, Raziye; Ma, Minh Thu; Güzel, Mustafa; Marasco, Daniela; Chadli, Ahmed; Gestwicki, Jason E.; Cowell, John K.; Wicha, Max S.; Hassan, Khaled A.; Korkaya, Hasan
    Following publication of this article the authors noted that the Acknowledgments section had been omitted. This section should read as follows.
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    Primary tumor-induced immunity eradicates disseminated tumor cells in syngeneic mouse model
    (Nature Publishing Group, 2019) Piranlıoğlu, Raziye; Lee, EunMi; Ouzounova, Maria; Bollag, Roni J.; Vinyard, Alicia H.; Arbab, Ali S.; Marasco, Daniela; Güzel, Mustafa; Cowell, John Kenneth; Thangaraju, Muthushamy; Chadli, Ahmed; Hassan, Khaled A.; Wicha, Max S.; Celis, Esteban; Körkaya, Hasan
    Although clinically apparent metastasis is associated with late stages of cancer development, micro-metastatic dissemination may be an early event. However, the fate of these early disseminated tumor cells (DTC) remains elusive. We show that despite their capacity to disseminate into secondary organs, 4T1 tumor models develop overt metastasis while EMT6-tumor bearing mice clear DTCs shed from primary tumors as well as those introduced by intravenous (IV) injection. Following the surgical resection of primary EMT6 tumors, mice do not develop detectable metastasis and reject IV-injected tumor cells. In contrast, these cells readily grow and metastasize in immuno-deficient athymic or Rag2(-/- )mice, an effect mimicked by CD8(+) T-cell depletion in immunocompetent mice. Furthermore, recombinant G-CSF or adoptive transfer of granulocytic-MDSCs isolated from 4T1 tumor-bearing mice, induce metastasis by suppressing CD8(+) T-cells in EMT6-primed mice. Our studies support the concept of immune surveillance providing molecular insights into the immune mechanisms during tumor progression.
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    The pleiotropic effects of TNF alpha in breast cancer subtypes is regulated by TNFAIP3/A20 (vol 38, pg 469, 2018)
    (Nature Publishing Group, 2019) Lee, Eunmi; Ouzounova, Maria; Piranlıoğlu, Raziye; Ma, Minh Thu; Güzel, Mustafa; Marasco, Daniela; Chadli, Ahmed; Gestwicki, Jason E.; Cowell, John Kenneth; Wicha, Max S.; Hassan, Khaled A.; Korkaya, Hasan
    Following publication of this article the authors noted that the Acknowledgments section had been omitted. This section should read as follows.
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    The pleiotropic effects of TNF? in breast cancer subtypes is regulated by TNFAIP3/A20
    (Nature Publishing Group, 2019) Lee, Eunmi; Ouzounova, Maria; Piranlıoğlu, Raziye; Ma, Minh Thu; Güzel, Mustafa; Marasco, Daniela; Chadli, Ahmed; Gestwicki, Jason E.; Cowell, John Kenneth; Wicha, Max S.; Hassan, Khaled A.; Korkaya, Hasan
    TNF alpha is a pleiotropic cytokine which fuels tumor cell growth, invasion, and metastasis in some malignancies, while in others it induces cytotoxic cell death. However, the molecular mechanism by which TNF alpha exerts its diverse effects on breast cancer subtypes remains elusive. Using in vitro assays and mouse xenografts, we show here that TNF alpha contributes to the aggressive properties of triple negative breast cancer (TNBC) cell lines via upregulation of TNFAIP3(A20). In a striking contrast, TNF alpha induces a potent cytotoxic cell death in luminal (ER+) breast cancer cell lines which fail to upregulate A20 expression. Overexpression of A20 not only protects luminal breast cancer cell lines from TNF alpha-induced cell death via inducing HSP70-mediated anti-apoptotic pathway but also promotes a robust EMT/CSC phenotype by activating the pStat3-mediated inflammatory signaling. Furthermore, A20 overexpression in luminal breast cancer cells induces aggressive metastatic properties in mouse xenografts via generating a permissive inflammatory microenvironment constituted by granulocytic-MDSCs. Collectively, our results reveal a mechanism by which A20 mediates pleiotropic effects of TNF alpha playing role in aggressive behaviors of TNBC subtype while its deficiency results in TNF alpha-induced apoptotic cell death in luminal breast cancer subtype.