Overexpression of TEAD4 in atypical teratoid/rhabdoid tumor: New insight to the pathophysiology of an aggressive brain tumor

BackgroundAtypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal brain tumor that occurs mainly in early childhood. Although most of the tumors are characterized by inactivating mutations of the tumor suppressor gene, SMARCB1, the biological basis of its tumorigenesis and aggressiveness is still unknown.ProcedureWe performed high‐throughput copy number variation analysis of primary cell lines generated from primary and relapsed tumors from one of our patients to identify new genes involved in AT/RT biology. The expression of the identified gene was validated in 29 AT/RT samples by gene expression profiling, quantitative real‐time polymerase chain reaction, and immunohistochemistry (IHC). Furthermore, we investigated the function of this gene by mutating it in rhabdoid tumor cells.ResultsTEAD4 amplification was detected in the primary cell lines and its overexpression was confirmed at mRNA and protein levels in an independent cohort of AT/RT samples. TEAD4’s co‐activator, YAP1, and the downstream targets, MYC and CCND1, were also found to be upregulated in AT/RT when compared to medulloblastoma. IHC showed TEAD4 and YAP1 overexpression in all samples. Cell proliferation and migration were significantly reduced in TEAD4‐mutated cells.ConclusionsWe report the overexpression of TEAD4 in AT/RT, which is a key component of Hippo pathway. Recent reports revealed that dysregulation of the Hippo pathway is implicated in tumorigenesis and poor prognosis of several human cancers. Our results suggest that TEAD4 plays a role in the pathophysiology of AT/RT, which represents a new insight into the biology of this aggressive tumor.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137309/1/pbc26398_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137309/2/pbc26398.pd

Differentiating comorbidities and predicting prognosis in idiopathic normal pressure hydrocephalus using cerebrospinal fluid biomarkers: a review

Idiopathic normal pressure hydrocephalus (iNPH) is a condition resulting from impaired cerebrospinal fluid (CSF) absorption and excretion characterized by a triad of symptoms comprising dementia, gait disturbance (impaired trunk balance), and urinary incontinence. CSF biomarkers not only assist in diagnosis but are also important for analyzing the pathology and understanding appropriate treatment indications. As the neuropathological findings characteristic of iNPH have yet to be defined, there remains no method to diagnose iNPH with 100% sensitivity and specificity. Neurotoxic proteins are assumed to be involved in the neurological symptoms of iNPH, particularly the appearance of cognitive impairment. The symptoms of iNPH can be reversed by improving CSF turnover through shunting. However, early diagnosis is essential as once neurodegeneration has progressed, pathological changes become irreversible and symptom improvement is minimal, even after shunting. Combining a variety of diagnostic methods may lead to a more definitive diagnosis and accurate prediction of the prognosis following shunt treatment. Identifying comorbidities in iNPH using CSF biomarkers does not contraindicate shunting-based intervention, but does limit the improvement in symptoms it yields, and provides vital information for predicting post-treatment prognosi

Pexophagy suppresses ROS-induced damage in leaf cells under high-intensity light

Although light is essential for photosynthesis, it has the potential to elevate intracellular levels of reactive oxygen species (ROS). Since high ROS levels are cytotoxic, plants must alleviate such damage. However, the cellular mechanism underlying ROS-induced leaf damage alleviation in peroxisomes was not fully explored. Here, we show that autophagy plays a pivotal role in the selective removal of ROS-generating peroxisomes, which protects plants from oxidative damage during photosynthesis. We present evidence that autophagy-deficient mutants show light intensity-dependent leaf damage and excess aggregation of ROS-accumulating peroxisomes. The peroxisome aggregates are specifically engulfed by pre-autophagosomal structures and vacuolar membranes in both leaf cells and isolated vacuoles, but they are not degraded in mutants. ATG18a-GFP and GFP-2×FYVE, which bind to phosphatidylinositol 3-phosphate, preferentially target the peroxisomal membranes and pre-autophagosomal structures near peroxisomes in ROS-accumulating cells under high-intensity light. Our findings provide deeper insights into the plant stress response caused by light irradiation

MMP-13 Promotes Tumor Angiogenesis

Background: Angiogenesis is an important step in the metastatic cascade of tumors. Results: MMP-13 itself as well as VEGF-A secretion from fibroblasts promotes angiogenesis. Indeed, MMP-13 is well correlated with blood vessel density in human cancer tissues. Conclusion: MMP-13 can be a marker for prediction of malignant behaviors and a therapeutic target in cancer. Significance: This work provides new insights regarding the role of MMP-13 in tumor angiogenesis

Odontogenic stem cells

Epithelial cell rests of Malassez (ERM) are quiescent epithelial remnants of the Hertwig’s epithelial root sheath (HERS) that are involved in the formation of tooth roots. ERM cells are unique epithelial cells that remain in periodontal tissues throughout adult life. They have a functional role in the repair/regeneration of cement or enamel. Here, we isolated odontogenic epithelial cells from ERM in the periodontal ligament, and the cells were spontaneously immortalized. Immortalized odontogenic epithelial (iOdE) cells had the ability to form spheroids and expressed stem cell-related genes. Interestingly, iOdE cells underwent osteogenic differentiation, as demonstrated by the mineralization activity in vitro in mineralization-inducing media and formation of calcification foci in iOdE cells transplanted into immunocompromised mice. These findings suggest that a cell population with features similar to stem cells exists in ERM and that this cell population has a differentiation capacity for producing calcifications in a particular microenvironment. In summary, iOdE cells will provide a convenient cell source for tissue engineering and experimental models to investigate tooth growth, differentiation, and tumorigenesis

2003b) A novel ER-derived compartment, the ER body, selectively accumulates b-glucosidase with an ER-retention signal in Arabidopsis

Summary The ER body is a novel compartment that is derived from endoplasmic reticulum (ER) in Arabidopsis. In contrast to whole seedlings which have a wide distribution of the ER bodies, rosette leaves have no ER bodies. Recently, we reported that wound stress induces the formation of many ER bodies in rosette leaves, suggesting that the ER body plays a role in the defense system of plants. ER bodies were visualized in transgenic plants (GFP-h) expressing green fluorescent protein (GFP) with an ER-retention signal, HDEL. These were concentrated in a 1000-g pellet (P1) of GFP-h plants. We isolated an Arabidopsis mutant, nai1, in which fluorescent ER bodies were hardly detected in whole plants. We found that a 65-kDa protein was specifically accumulated in the P1 fraction of GFP-h plants, but not in the P1 fraction of nai1 plants. N-terminal peptide sequencing revealed that the 65-kDa protein was a b-glucosidase, PYK10, with an ER-retention signal, KDEL. Immunocytochemistry showed that PYK10 was localized in the ER bodies. Compared with the accumulation of GFP-HDEL, which was associated with both cisternal ER and ER bodies, the accumulation of PYK10 was much more specific to ER bodies. PYK10 was one of the major proteins in cotyledons, hypocotyls and roots of Arabidopsis seedlings, while PYK10 was not detected in rosette leaves that have no ER bodies. These findings indicated that PYK10 is the main component of ER bodies. It is possible that PYK10 produces defense compounds when plants are damaged by insects or wounding