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// Cui-Ling Ding 1,* , Gang Xu 1,* , Hai-Lin Tang 1 , Shi-Ying Zhu 1 , Lan-Juan Zhao 1 , Hao Ren 1 , Ping Zhao 1 , Zhong-Tian Qi 1 and Wen Wang 1 1 Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Zhong-Tian Qi, email: // Wen Wang, email: // Keywords : RAI16, Fam160B2, AKAP, PKA-RIIα, 14-3-3θ Received : January 19, 2015 Accepted : March 05, 2015 Published : March 30, 2015 Abstract Our previous study reported that retinoic acid induced 16 (RAI16) could enhance tumorigenesis in hepatocellular carcinoma (HCC). However, the cellular functions of RAI16 are still unclear. In this study, by immunoprecipitation and tandem (MS/MS) mass spectrometry analysis, we identified that RAI16 interacted with the type II regulatory subunit of PKA (PKA-RIIα), acting as a novel protein kinase A anchoring protein (AKAP). In addition, RAI16 also interacted with heat shock protein 70 (HSP70) and 14-3-3θ. Further studies indicated that RAI16 mediated PKA phosphorylation of HSP70 at serine 486, resulting in anti-apoptosis events. RAI16 was also phosphorylated by the anchored PKA at serine 325, which promoted the recruitment of 14-3-3θ, which, in turn, inhibited RAI16 mediated PKA phosphorylation of HSP70. These findings offer mechanism insight into RAI16 mediated anti-apoptosis signaling in HCC.

// Nanlin Li 1,* , Hui Wang 1,* , Jing Fan 1 , Chao Tong 1 , Jixin Yang 1 , Hongliang Wei 1 , Jun Yi 1 , Rui Ling 1 1 Department of Vascular and Endocrine Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, China * These authors contributed equally to the work Correspondence: Rui Ling, email: // Nanlin Li, email: // Keywords : 14-3-3θ, Breast Cancer, Metastasis, Prognosis Received : October 14, 2013 Accepted : December 3, 2013 Published : December 5, 2013 Abstract An isoform of the 14-3-3 protein family, 14-3-3θ has been linked with tumor cell proliferation and apoptosis. However, the role of 14-3-3θ in the progression of breast cancer remains unknown. Here, we report that 14-3-3θ plays a critical role in breast cancer metastasis and prognosis. The expression of 14-3-3θ was markedly higher in breast cancer tissues compared to adjacent normal tissues. A hospital-based study cohort of 216 breast cancer patients was evaluated in this study. The level of 14-3-3θ expression was determined and correlated based upon tumor clinicopathological features, disease-free survival, and overall survival. We found that overexpression of 14-3-3θ was correlated with advanced TNM stage (P < 0.05), lymph node metastasis (P < 0.05), and ER negative status (P < 0.05). Breast cancer patients with high 14-3-3θ expression had a shorter overall survival and a higher rate of recurrence than those with low 14-3-3θ expression. Additionally, knockdown of 14-3-3θ expression in breast cancer cells inhibited metastasis in vitro. Similarly, an in vivo assay showed that 14-3-3θ knockdown dramatically suppressed the growth of breast cancer xenografts and inhibited tumor cell metastasis in a lung metastasis model. Thus, this study provided the first evidence that 14-3-3θ is a novel tumor suppressor and may serve as a candidate prognostic biomarker and target for new therapies in metastatic breast cancer.