Overexpression of Oct4, a stemness gene encoding a transcription factor, has been reported in several cancers. However, the mechanism by which Oct4 directs transcriptional program that leads to somatic cancer progression remains unclear. In this study, we provide mechanistic insight into Oct4-driven transcriptional network promoting drug-resistance and metastasis in lung cancer cell, animal and clinical studies. Through an integrative approach combining our Oct4 chromatin-immunoprecipitation sequencing and ENCODE datasets, we identified the genome-wide binding regions of Oct4 in lung cancer at promoter and enhancer of numerous genes involved in critical pathways which promote tumorigenesis. Notably, PTEN and TNC were previously undefined targets of Oct4. In addition, novel Oct4-binding motifs were found to overlap with DNA elements for Sp1 transcription factor. We provided evidence that Oct4 suppressed PTEN in an Sp1-dependent manner by recruitment of HDAC1/2, leading to activation of AKT signaling and drug-resistance. In contrast, Oct4 transactivated TNC independent of Sp1 and resulted in cancer metastasis. Clinically, lung cancer patients with Oct4 high, PTEN low and TNC high expression profile significantly correlated with poor disease-free survival. Our study reveals a critical Oct4-driven transcriptional program that promotes lung cancer progression, illustrating the therapeutic potential of targeting Oc4 transcriptionally regulated genes.
Young children's visual environments are dynamic, changing moment-by-moment as children physically and visually explore spaces and objects and interact with people around them. Headmounted eye tracking offers a unique opportunity to capture children's dynamic egocentric views and how they allocate visual attention within those views. This protocol provides guiding principles and practical recommendations for researchers using head-mounted eye trackers in both laboratory and more naturalistic settings. Head-mounted eye tracking complements other experimental methods by enhancing opportunities for data collection in more ecologically valid contexts through increased portability and freedom of head and body movements compared to screen-based eye tracking. This protocol can also be integrated with other technologies, such as motion tracking and heart-rate monitoring, to provide a high-density multimodal dataset for examining natural behavior, learning, and development than previously possible. This paper illustrates the types of data generated from head-mounted eye tracking in a study designed to investigate visual attention in one natural context for toddlers: free-flowing toy play with a parent. Successful use of this protocol will allow researchers to collect data that can be used to answer questions not only about visual attention, but also about a broad range of other perceptual, cognitive, and social skills and their development.
Coordinated attention between children and their parents plays an important role in their social, language, and cognitive development. The current study used head‐mounted eye‐trackers to investigate the effects of children's prelingual hearing loss on how they achieve coordinated attention with their hearing parents during free‐flowing object play. We found that toddlers with hearing loss (age: 24–37 months) had similar overall gaze patterns (e.g., gaze length and proportion of face looking) as their normal‐hearing peers. In addition, children's hearing status did not affect how likely parents and children attended to the same object at the same time during play. However, when following parents' attention, children with hearing loss used both parents' gaze directions and hand actions as cues, whereas children with normal hearing mainly relied on parents' hand actions. The diversity of pathways leading to coordinated attention suggests the flexibility and robustness of developing systems in using multiple pathways to achieve the same functional end.
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