Mounting evidence indicates that hotspot p53 mutant proteins often possess gain-of-function property in promoting cell mobility and tumor metastasis. However, the molecular mechanisms are not totally understood. In this study, we demonstrate that the hotspot mutation, p53-R273H, promotes cell migration, invasion in vitro and tumor metastasis in vivo. p53-R273H significantly represses expression of DLX2, a homeobox protein involved in cell proliferation and pattern formation. We show that p53-R273H-mediated DLX2 repression leads to upregulation of Neuropilin-2 (NRP2), a multifunctional co-receptor involved in tumor initiation, growth, survival and metastasis. p53-R273H-induced cell mobility is effectively suppressed by DLX2 expression. Furthermore, knockdown of NRP2 significantly inhibits p53-R273H-induced tumor metastasis in xenograft mouse model. Together, these results reveal an important role for DLX2-NRP2 in p53-R273H-induced cell mobility and tumor metastasis.

Hotspot p53 mutant proteins often gain novel functions in promoting tumor metastases. However, the molecular mechanisms by which mutant p53 exerts gain-of-function in cancer are not totally understood. In this study, we demonstrate that hotspot mutant p53, p53-R273H, promotes cell scattering growth and migration via inhibiting the expression of Krupple-like factor 6 (KLF6), a Zinc finger transcription factor and a documented tumor suppressor. Restoration of KLF6 increases the expression of E-cadherin downregulated by p53-R273H and inhibits p53-R273Hinduced cell migration and tumor metastasis. Further, p53-R273H reduces KLF6 transcription by upregulating EGFR expression which in turn activates AKT-FOXO1 axis. Pharmacological inhibitor of AKT, MK2206, rescues KLF6 expression and suppresses p53-R273H-induced cell migration. Clinical analyses reveal that KLF6 expression is decreased in human breast cancer specimens harboring p53 mutations, and negatively correlated with EGFR expression in human breast cancer. In addition, low expression of KLF6 is associated with poor overall survival (OS) and relapse-free survival (RFS) in p53 mutated human breast cancer patients. Together, these results reveal an important role for EGFR-AKT-FOXO1-KLF6-E-cadherin axis in mutant p53-induced cell migration and tumor metastasis.

Although great accomplishments of in situ conservation have been made during the last decade throughout the world, there is an urgent need to conduct more targeted research to explore many basic questions about crop wild relatives (CWR) <i>in situ</i> conservation such as how to better identify and manage the target <i>in situ</i> conservation populations of CWR. In this study, we performed an extensive field investigation of 201 natural populations or habitats of O. <i>rufipogon</i>, a seriously endangered wild progenitor of cultivated rice in China. Our updated information suggests that: 1) the majority of the natural populations have been extinct throughout China, which leads to serious fragmentation of the population system as a whole; and 2) the survived populations have become small in size and thus fragmented within the population as a result of the loss of subpopulations. To assess the relationships between the biodiversity education and conservation of wild rice, we employed participatory approaches in the field investigation. Our data indicate that the continuous rapid decline of biodiversity education seemed closely related to the extinction of wild rice germplasm. These findings imply the potential necessity and huge challenge for making <i>in situ</i> conservation plans in the future. By means of our understanding of ecogeography, sociology and culture, and population genetics of the species, we propose a strategy for selecting <i>in situ</i> conservation locations as well as priority sites for establishing <i>in situ</i> conservation practices in China

The three rights separation reform (TRSR) has laid a concrete foundation institutionally to guide the well-ordered transfer of farmland and promoting the development of urbanization. With the new economics of labour migration (hereinafter referred to as the NELM) theory as the analytic basis, this empirical research investigates the potential ramifications of off-farm employment on land efficiency with household-based survey data from four provinces in China after TRSR. Unlike existing studies, we delve into how the effects are manifested differently among the types of off-farm employment by adopting an ordinary least squares (OLS) model and a two-stage least squares (2SLS) estimator. It provides evidence that migration positively affect land efficiency significantly, whereas a negative impact of local off-farm employment on land efficiency is observed, which distinct this study from previous findings. From the perspective of policy-making, land administrators should realize that off-farm employment differentiation is an important factor affecting land efficiency, and therefore needs to be fully considered in policy-making. Meanwhile, the establishment of local labor markets and favorable policies that stimulate productive technologies are needed.

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