BackgroundEndometrial cancer is one of the most common gynecological malignancies and has exhibited an increasing incidence rate in recent years. Cancer stem cells (CSCs), which are responsible for tumor growth and chemoresistance, have been confirmed in endometrial cancer. However, it is still challenging to identify endometrial cancer stem cells to then target for therapy.MethodsFlow cytometry was used to identify the endometrial cancer stem cells. Sphere formation assay, western blotting, qRT-PCR assay, cell viability assay, xenograft assay and immunohistochemistry staining analysis were utilized to evaluate the effect of SPARC-related modular calcium binding 2 (SMOC-2) on the cells proliferation and drug resistance. Cell viability assay, qRT-PCR assay, immunofluorescence staining, Co-IP assay and luciferase reporter gene assay were performed to explore the possible molecular mechanism by which SMOC-2 activates WNT/β-catenin pathway.FindingsWe found the expression of SPARC-related modular calcium binding 2 (SMOC-2), a member of SPARC family, was higher in endometrial CSCs than that in non-CSCs. SMOC-2 was also more highly expressed in spheres than in monolayer cultures. The silencing of SMOC-2 suppressed cell sphere ability; reduced the expression of the stemness-associated genes SOX2, OCT4 and NANOG; and enhanced chemosensitivity in endometrial cancer cells. By co-culture IP assay, we demonstrated that SMOC-2 directly interacted with WNT receptors (Fzd6 and LRP6), enhanced ligand-receptor interaction with canonical WNT ligands (Wnt3a and Wnt10b), and finally, activated the WNT/β-catenin pathway in endometrial cancer. SMOC-2 expression was closely correlated with CSC markers CD133 and CD44 expression in endometrial cancer tissue.InterpretationTaken together, we conclude that SMOC-2 might be a novel endometrial cancer stem cell signature gene and therapeutic target for endometrial cancer.FundNational Natural Science Foundation of China, Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission, Scientific and Technological Innovation Act Program of Fengxian Science and Technology Commission, Natural Science Foundation of Shanghai.

Phosphorus (P) is a key limiting nutrient in subtropical forests and mixed forests with broadleaved species have been expected to stimulate P cycling, compared to pure conifer plantations. However, the mixture effect of Chinese fir (Cunninghamia lanceolata (Lamb.) Hook.) and broadleaved species on rhizosphere soil and coniferous tree P dynamics is unclear. In our study, eight plots of a single species of a Chinese fir plantation (pure plantation, PP) and eight mixed plantations (mixed plantation, MP) with broadleaved tree species (Michelia macclurei Dandy in Hunan Province or Schima superba Gardn. et Champ. in Fujian Province) were selected in subtropical China. Six P fractions in the rhizosphere and bulk soils were analyzed by a modified Hedley P fractionation method. Phosphorus fractions and nitrogen (N) concentrations in different root orders, different age fresh needles and twigs, and needle and twig litter of Chinese fir were measured. Our results showed that available P, slowly released P, occluded P, and the total extractable P in rhizosphere soil were significantly higher in MP than PP (p < 0.05). In contrast, P and N concentrations in the transportive roots and two-year old needles were generally higher in PP than MP. Meanwhile, the slowly released P, occluded P, total extractable P, and residual P in rhizosphere soil were negatively correlated with P concentrations in young (absorptive and transportive roots, one- and two-year old needles) but not old tissues (storative roots, three-year old needles and litters). In conclusion, mixture may increase soil P availability through the rhizosphere effect, but can decrease P and N concentration of Chinese fir tissues by competition between Chinese fir and broadleaved species. Clearly, the mixture effect may differ in soil and plant nutrients, and this issue needs be taken into consideration when converting a pure conifer plantation into a mixed-species forest.