Purpose: Prospero homeobox 1 (PROX1) has been shown to function as a tumor suppressor in various types of cancer. However, it promotes colon cancer progression. The aim of this study is to clarify the underlying mechanism by which PROX1 regulates tumorigenicity of colon cancer.Experimental Design: Association of PROX1 and clinicopathological features was studied by immunohistochemical staining. Pri-miR-9-2 and miR-9 were detected by quantitative real-time PCR. Assays of cell invasion, adhesion, and matrix metalloproteinase activity were used to study PROX1-mediated epithelialmesenchymal transition (EMT).Results: PROX1 was overexpressed in 43% (59/136) of colon cancer tissues and its expression was correlated with E-cadherin downregulation (P ¼ 0.00005), advanced tumor staging (P ¼ 0.005), and lymph node metastasis (P ¼ 0.000009). Enforced expression of PROX1 in DLD-1 cells caused downregulation of Ecadherin and integrins and attenuated cell adhesion. These cells showed increase of matrix metalloproteinase activity and invasive ability. Conversely, knockdown of PROX1 in SW620 cells restored E-cadherin protein expression and reduced invasiveness. Unexpectedly, repression of E-cadherin by PROX1 was not mediated by transcriptional inhibition. We found that PROX1 bound to miR-9-2 promoter and triggered its expression to suppress E-cadherin 3 0 UTR reporter activity and protein expression. Anti-miR-9 restored Ecadherin in SW620 cells, whereas precursor miR-9 inhibited E-cadherin in PROX1-knockdown cells. The miR-9 level was higher in tumor tissues with high PROX1/low E-cadherin than that of tumor tissues with low PROX1/high E-cadherin. Conclusions: Our results provide mechanistic insights by which PROX1 promotes EMT and colon cancer progression. Targeting of PROX1-mediated oncogenic activity may be helpful for the treatment of colon cancer. Clin Cancer Res; 18(23); 6416-25. Ó2012 AACR.
This paper presents an efficient opportunistic retransmission protocol (PRO, Protocol for Retransmitting Opportunistically) to improve the performance of IEEE 802.11 WLANs. PRO is a link-layer protocol that allows overhearing nodes to function as relays that retransmit on behalf of the source af ter they learn about a failed transmission. Relays with stronger connectivity to the destination have a higher chance of delivering the packet than the source does, thereby resulting in a more efficient use of the channel. PRO has four main features. First, channel reciprocity coupled with a run-time calibration process is used to estimate the instantaneous link quality to the destination. Second, a local qualification process filters out poor relays early. Third, a distributed relay selection algorithm chooses the best set of eligible relays among all qualified relays and prioritizes them. Finally, 802.11e Enhanced Distributed Channel Access (EDCA) is leveraged to make sure high priority relays transmit with high probability. PRO is designed to coexist with legacy 802.11 stations. We have implemented PRO in the driver of a commodity wireless card. Our extensive evaluation on both a controlled testbed and in the real world shows that PRO boosts throughput in diverse wireless environments, and especially in when there is significant contention for the channels, under fading, and with user mobility.
Robust video streaming over time-varying, error-prone wireless LANs (WLANs) poses many challenges. In this paper, we present a Time-based Opportunistic Relay (TOR) scheme for high-quality video streaming over WLANs. The proposed scheme exploits path diversity in relaying packets with awareness of the time constraints of video data. Specifically, relay nodes continuously overhear and opportunistically forward packets to enhance end-to-end delivery rates. To relay a packet in a time-aware manner, a relay deadline is computed for each packet and used by relay nodes to determine whether they should relay or discard the packet. Simulation results show that TOR improves video quality by up to 9.76 dB.
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