Advances of targeting the YAP/TAZ-TEAD complex in the hippo pathway for the treatment of cancers.

The Hippo pathway is an evolutionarily conserved signaling pathway that plays critical roles in the tumorigenesis and progression of breast cancer, oral cancer, rectal cancer, colloid cancer, and so on. YAP/TAZ-TEAD complex is a key knot in the Hippo pathway regulating cell proliferation and stem cell functions. Activation or overexpression of this complex has been proved to lead to cell transformation, proliferation and eventually cancerization. In this review, the association between the alterations of hippo pathway and tumorigenesis of various cancer had been elucidated. The structural basis of YAP/TAZ-TEAD complex is analyzed, and the targeting inhibitors are summarized within the medicinal chemistry classification. Moreover, we have also discussed the clinical status and current challenges of these drug candidates, and provide guidance for the future development of inhibitors targeting this pathway, especially YAP/TAZ-TEAD complex.

Metabolomics Reveals the Response of the Phenylpropanoid Biosynthesis Pathway to Starvation Treatment in the Grape Endophyte Alternaria sp. MG1.

Phenylpropanoid (PPPN) compounds are widely used in agriculture, medical, food, and cosmetic industries because of their multiple bioactivities. Alternaria sp. MG1, an endophytic fungus isolated from grape, is a new natural source of PPPNs. However, the PPPN biosynthesis pathway in MG1 tends to be suppressed under normal growth conditions. Starvation has been reported to stimulate the PPPN pathway in plants, but this phenomenon has not been well studied in endophytic fungi. Here, metabolomics analysis was used to examine the profile of PPPN compounds, and quantitative reverse transcription-polymerase chain reaction was used to detect the expression of key genes in the PPPN biosynthesis pathway under starvation conditions. Starvation treatment significantly increased the accumulation of shikimate and PPPN compounds and upregulated the expression of key genes in their biosynthesis pathways. In addition to previously reported PPPNs, sinapate, 4-hydroxystyrene, piceatannol, and taxifolin were also detected under starvation treatment. These findings suggest that starvation treatment provides an effective way to optimize the production of PPPN compounds and may permit the investigation of compounds that are undetectable under normal conditions. Moreover, the diversity of its PPPNs makes strain MG1 a rich repository of valuable compounds and an extensive genetic resource for future studies.

Production of pinoresinol diglucoside, pinoresinol monoglucoside, and pinoresinol by Phomopsis sp. XP-8 using mung bean and its major components.

Phomopsis sp. XP-8 is an endophytic fungus that has the ability to produce pinoresinol diglucoside (PDG) in vitro and thus has potential application for the biosynthesis of PDG independent of plants. When cultivated in mung bean medium, PDG production was significantly improved and pinoresinol monoglucoside (PMG) and pinoresinol (Pin) were also found in the culture medium. In this experiment, starch, protein, and polysaccharides were isolated from mung beans and separately used as the sole substrate in order to explore the mechanism of fermentation and identify the major substrates that attributed to the biotransformation of PDG, PMG, and Pin. The production of PDG, PMG, and Pin was monitored using high-performance liquid chromatography (HPLC) and confirmed using HPLC-MS. Activities of related enzymes, including phenylalanine ammonia-lyase (PAL), trans-cinnamate 4-hydroxylase (C4H), and 4-coumarate-CoA ligase (4CL) were analyzed and tracked during the cultivation. The reaction system contained the compounds isolated from mung bean in the designed amount. Accumulation of phenylalanine, cinnamic acid, p-coumaric acid, PDG, PMG, and Pin and the activities of PAL, C4H, and 4CL were measured during the bioconversion. PMG was found only when mung bean polysaccharide was analyzed, while production of PDG and Pin were found when both polysaccharide and starch were analyzed. After examining the monosaccharide composition of the mung bean polysaccharide and the effect of the different monosaccharides had on the production of PMG, PDG, and Pin, galactose in mung bean polysaccharide proved to be the major factor that stimulates the production of PMG.