Blockade of Fas signaling in breast cancer cells suppresses tumor growth and metastasis via disruption of Fas signaling-initiated cancer-related inflammation
Authors: Qiuyan Liu
Cheng Qian
Yuanyuan Zheng
Qingqing Wang
Nan Li
Xuetao Cao
Qinchun Tan
Kun Chen
Journal: Journal of Biological Chemistry (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Breast Cancer; Fas; IL-6; Inflammation; MDSC
Affiliations: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China,. Electronic address: ., Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China, and., National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China., National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China,; Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China, and; National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China. Electronic address: .

Abstract:  Mechanisms for cancer-related inflammation remain to be fully elucidated. Non-apoptotic functions of Fas signaling have been proposed to play an important role in promoting tumor progression. It has yet to be determined if targeting Fas signaling can control tumor progression through suppression of cancer-related inflammation. In the current study we found that breast cancer cells with constitutive Fas expression were resistant to apoptosis induction by agonistic anti-Fas antibody (Jo2) ligation or Fas ligand cross-linking. Higher expression of Fas in human breast cancer tissue has been significantly correlated with poorer prognosis in breast cancer patients. To determine whether blockade of Fas signaling in breast cancer could suppress tumor progression, we prepared an orthotopic xenograft mouse model with mammary cancer cells 4T1 and found that blockade of Fas signaling in 4T1 cancer cells markedly reduced tumor growth, inhibited tumor metastasis in vivo, and prolonged survival of tumor-bearing mice. Mechanistically, blockade of Fas signaling in cancer cells significantly decreased systemic or local recruitment of myeloid derived suppressor cells (MDSCs) in vivo. Furthermore, blockade of Fas signaling markedly reduced IL-6, prostaglandin E2 production from breast cancer cells by impairing p-p38, and activity of the NFκB pathway. In addition, administration of a COX-2 inhibitor and anti-IL-6 antibody significantly reduced MDSC accumulation in vivo. Therefore, blockade of Fas signaling can suppress breast cancer progression by inhibiting proinflammatory cytokine production and MDSC accumulation, indicating that Fas signaling-initiated cancer-related inflammation in breast cancer cells may be a potential target for treatment of breast cancer. 

Retracted: No

PubPeer comments:
 Posting for another reader, about concerns in Figures 1 and 6. Figure 1. * In green: two lanes in the Fas panel of Figure 1A look similar to two lanes in the Fas panel of Figure 1C. * In red: two lanes in the GAPDH panel of Figure 1A look similar to two lanes in the GAPDH panel of Figure 1C. ![file] , 
 Figure 6, Nu65 panel. * In blue: Lanes 2-4 look similar to lanes 5-7. ![file] , 
 2020 Expression of Concern. https: www.jbc.org content 295 26 8886 The publisher of the Journal of Biological Chemistry is issuing an Expression of Concern to inform readers that credible concerns have been raised regarding some of the data and conclusions in the article listed above. The Journal of Biological Chemistry will provide additional information as it becomes available. , 
 Retraction on Jan 1, 2021, published online May 22, 2021 https: www.jbc.org article S0021-9258(21)00550-0 fulltext Withdrawal: Blockade of Fas signaling in breast cancer cells suppresses tumor growth and metastasis via disruption of Fas signaling-initiated cancer-related inflammation This article has been withdrawn by the authors. The Journal states that lanes 1 and 2 in the Fas panel immunoblot in Fig. 1A were reused in lanes 2 and 3 of Fas panel immunoblot in Fig. 1C. Lanes 2 and 3 in GAPDH panel immunoblot in Fig. 1A were reused in lanes 1 and 2 of GAPDH panel immunoblot in Fig. 1C. In Fig. 6D, lanes 2 to 4 were duplicated in lanes 5 to 7 of the Nu65 immunoblot. The authors are able to retrieve all raw data and offer to update the respected panels using the same raw images again or those from experiments under the same conditions. The offer was declined by the Journal. The authors state that the above issues do not affect the interpretation of the data nor conclusions of this research study. The authors state that the activation of NF-u03baB signal pathways by Fas signaling reported in this article has been confirmed in breast cancer and other types of cancer by other independent studies. The authors have indicated that they plan to submit this work elsewhere for publication. ,