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Cell migration-inducing protein (CEMIP) and binding immunoglobulin protein (BiP) are upregulated in human cancers, where they drive cancer progression and metastasis. It has been shown that CEMIP resides in the endoplasmic reticulum (ER) where it interacts with BiP to induce cell migration, but the relationship between the two proteins was previously unknown. Here we show that CEMIP mediates activation of the BiP promoter and upregulates BiP transcript and protein levels in breast cancer cell lines. Moreover, CEMIP overexpression confers protective adaptations to cancer cells under hypoxic conditions, by decreasing apoptosis, activating autophagy, and increasing glucose uptake, to facilitate tumor growth. We demonstrate that BiP signals downstream of CEMIP, modulating cellular resistance to hypoxia. Reducing BiP in CEMIP-expressing cells sensitized cells to hypoxia treatment, decreased glucose uptake, and resulted in tumor regression in vivo. Our study provides insights into the link between CEMIP and BiP expression and the pro-survival role they play in hypoxia. Better understanding of the mechanisms behind cancer cell adaptations to harsh tumor environments could lead to development of improved cancer treatments.

// Xiangrui Ma 1, 2, * , Surui Sheng 1, * , Jingbiao Wu 1, * , Yaping Jiang 1, 3 , Xiaolei Gao 1 , Xiao Cen 1 , Jiashun Wu 1 , Shasha Wang 1 , Yajie Tang 4 , Yaling Tang 1, 5 and Xinhua Liang 1, 6 1 State Key Laboratory of Oral Diseases, West China Hospital of Stomatology (Sichuan University), Chengdu, Sichuan 610041, China 2 Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256600, China 3 Department of Implant, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, China 4 Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan, Hubei 430068, China 5 Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu, Sichuan 610041, China 6 Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, Sichuan 610041, China * These authors have contributed equally to this work Correspondence to: Yaling Tang, email: tangyaling@scu.edu.cn Xinhua Liang, email: lxh88866@scu.edu.cn Keywords: head and neck squamous cell carcinomas (HNSCC), human papillomavirus (HPV), the non-coding RNA (lncRNA), myeloid-derived suppressor cells (MDSCs) Received: November 08, 2016 Accepted: December 27, 2016 Published: February 01, 2017 ABSTRACT The emerging evidence showed that long noncoding RNAs (lncRNAs) are involved in cell growth and apoptosis as well as cancer progression and metastasis of malignant tumor, however, limited data are available on the role of lncRNAs in human papillomavirus (HPV)-associated Head and neck squamous cell carcinomas (HNSCC). Here, we demonstrated that 23.98% of 196 HNSCC cases in Southwest China could be classified as HPV16 infection. The number of MDSCs in HPV-positive HNSCC was significantly higher than normal control, indicating that HPV infection may promote MDSCs aggregation. Then, we applied an array-based approach to monitor the lncRNA expression between HPV-positive HNSCC, HPV-negative HNSCC and normal oral mucous, and obtained 132 different lncRNAs in different HPV infected states of HNSCC. HOTAIR, PROM1, CCAT1, and MUC19 mRNA levels, determined by qRT-PCR were inversely correlated with MDSCs collection of HPV-associated HNSCC in 2 independent patient cohorts. The results may provide a rationale for the further evaluation of lncRNAs as a molecular target to elucidate the molecular mechanism of HPV promoting MDSCs collection of HNSCC.

Cancer stem cells (CSCs) have gained much attention due to their roles in the invasion and metastasis of numerous kinds of human cancers. Here, we showed that the positive expression of CD133, the stemness marker, was positively associated with vasculogenic mimicry (VM) formation, local regional recurrence, distant metastasis and poorer prognosis in salivary adenoid cystic carcinoma (ACC) specimens. Compared with CD133- ACC cells, CD133+ cancer stem-like cells had more migration and invasion capabilities, as well as more VM formation. The levels of endothelial cell marker VE-cadherin, MMP-2 and MMP-9 expression in CD133+ cancer stem-like cells and xenograft tumors of nude mice injected with CD133+ cells were significantly higher than those with CD133- cells. The data indicated that CD133+ cancer stem-like cells might contribute to the migration and invasion of ACC through inducing VM formation.

// Ya-ling Tang 1, 2 , Xin Liu 2 , Shi-yu Gao 2 , Hao Feng 2 , Ya-ping Jiang 2 , Sha-sha Wang 2 , Jing Yang 2 , Jian Jiang 2 , Xiang-rui Ma 2 , Ya-jie Tang 3 , Yu Chen 1 , Xin-hua Liang 2, 4 1 Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People’s Republic of China 2 State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People’s Republic of China 3 Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, People’s Republic of China 4 Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People’s Republic of China Correspondence to: Xin-hua Liang, e-mail: lxh88866@scu.edu.cn , drliangxinhua@aliyun.com Keywords: wild-type p53 induced phosphatase 1 (WIP1), adenoid cystic carcinoma (ACC), salivary gland, invasion, metastasis Received: January 09, 2015 Accepted: February 23, 2015 Published: March 06, 2015 ABSTRACT The wild-type p53 induced phosphatase 1 (WIP1) is an oncogene overexpressed in a variety of human cancers. Here, we demonstrated that WIP1 silencing reduced MMP-9 and VEGF-C expression as well as migration and invasion of salivary adenoid cystic carcinoma (ACC) cells. Overexpression of MMP-9 or VEGF-C restored migration and invasion in WIP1 knockdown cells, indicating that MMP-9 and VEGF-C are downstream targets of WIP1 signaling. Levels of cyclin D1 and c-Myc, targets of Wnt/β-catenin pathway, were significantly decreased by WIP1 silencing. In addition, WIP1 expression was positively associated with metastasis and prognosis of ACC patients as well as with MMP-9 or VEGF-C in ACC tissues.

// Min Zheng 1, 2, * , Ya-ping Jiang 1, * , Wei Chen 1, 3, * , Kai-de Li 1 , Xin Liu 1 , Shi-yu Gao 1 , Hao Feng 1 , Sha-sha Wang 1 , Jian Jiang 1 , Xiang-rui Ma 1 , Xiao Cen 1 , Ya-jie Tang 4 , Yu Chen 1 , Yun-feng Lin 1 , Ya-ling Tang 1, 5 , Xin-hua Liang 1, 6 1 State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China 2 Department of Stomatology, Zhoushan Hospital, Zhoushan, Zhejiang 316000, People's Republic of China 3 Department of Oral and Maxillofacial Surgery, Tianjin Stomatological Hospital, Tianjin 300041, People's Republic of China 4 Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, People's Republic of China 5 Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China 6 Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China * These authors have contributed equally to this work Correspondence to: Ya-ling Tang, e-mail: tangyaling@scu.edu.cn Xin-hua Liang, e-mail: lxh88866@scu.edu.cn ; drliangxinhua@aliyun.com Keywords: Oral tongue squamous cell carcinoma (OTSCC), Epithelial-mesenchymal transition (EMT), miR-101, Snail, Slug Received: November 03, 2014 Accepted: January 25, 2015 Published: February 09, 2015 ABSTRACT microRNAs(miRNAs) can regulate epithelial-mesenchymal transition (EMT) through transcription factors, however, little is known whether EMT transcription factors can modulate miRNAs and further induce EMT and cancer metastasis. Here we show that overexpression of Snail and Slug leads to a mesenchymal phenotype and morphology and enhances cell invasion along with stem cell properties in squamous cell carcinoma of oral tongue (OTSCC) cells. Repression of miR-101 expression by Snail and Slug is essential for Snail/Slug-induced malignant phenotypes. The suppression of miR-101 subsequently activates EZH2, the sole histone methyltransferase, inducing EMT, migration and invasion of OTSCC cells. Importantly, co-overexpression of Slug and Snail correlates with poor survival and elevated EZH2 expression in two independent patient cohorts of OTSCC specimens. These findings defined a Snail and Slug/miR-101/EZH2 pathway as a novel regulatory axis of EMT-mediated-microRNA signaling.

// Ming-xin Cao 1,2 , Ya-ping Jiang 3 , Ya-ling Tang 1,4 and Xin-hua Liang 1,2 1 State Key Laboratory of Oral Diseases, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan, People’s Republic of China 2 Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan, People’s Republic of China 3 Department of Implant, The Affiliated Hospital of Qingdao University, Qingdao,Shandong, People’s Republic of China 4 Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan, People’s Republic of China Correspondence to: Xin-hua Liang, email: // Ya-ling Tang, email: // Keywords : lncRNA, microRNA, epithelial-mesenchymal plasticity, cancer metastasis Received : October 15, 2016 Accepted : December 12, 2016 Published : December 15, 2016 Abstract Noncoding RNAs (ncRNAs) have been demonstrated to closely associate with gene regulation and encompass the well-known microRNAs (miRNAs), as well as the most recently acknowledged long noncoding RNAs (lncRNAs). Current evidence indicates that lncRNAs can interact with miRNAs and these interactions play crucial roles in cancer metastasis, through regulating critical events especially the epithelial-mesenchymal transition (EMT). This review summarizes the types of lncRNA-miRNA crosstalk identified to-date and discusses their influence on the epithelial-mesenchymal plasticity and clinical metastatic implication.