Browsing by Author "Wei, Yiju"

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Open Access
Differential YAP expression in glioma cells induces cell competition and promotes tumorigenesis.
(Journal of cell science, 2019-03-04) Liu, Zhijun; Yee, Patricia P; Wei, Yiju; Liu, Zhenqiu; Kawasawa, Yuka Imamura; Li, Wei
Intratumor heterogeneity associates with cancer progression and may account for a substantial portion of therapeutic resistance. Although extensive studies have focused on the origin of the heterogeneity, biological interactions between heterogeneous malignant cells within a tumor are largely unexplored. Glioblastoma (GBM) is the most aggressive primary brain tumor. Here, we found that the expression of Yes-associated protein (YAP, also known as YAP1) is intratumorally heterogeneous in GBM. In a xenograft mouse model, differential YAP expression in glioma cells promotes tumorigenesis and leads to clonal dominance by cells expressing more YAP. Such clonal dominance also occurs in vitro when cells reach confluence in the two-dimensional culture condition or grow into tumor spheroids. During this process, growth of the dominant cell population is enhanced. In the tumor spheroid, such enhanced growth is accompanied by increased apoptosis in cells expressing less YAP. The cellular interaction during clonal dominance appears to be reminiscent of cell competition. RNA-seq analysis suggests that this interaction induces expression of tumorigenic genes, which may contribute to the enhanced tumor growth. These results suggest that tumorigenesis benefits from competitive interactions between heterogeneous tumor cells.
Open Access
Induction of store-operated calcium entry (SOCE) suppresses glioblastoma growth by inhibiting the Hippo pathway transcriptional coactivators YAP/TAZ
(Oncogene, 2019-01) Liu, Zhijun; Wei, Yiju; Zhang, Lei; Yee, Patricia P; Johnson, Martin; Zhang, Xuexin; Gulley, Melissa; Atkinson, Jennifer M; Trebak, Mohamed; Wang, Hong-Gang; Li, Wei
Open Access
Neutrophil-induced ferroptosis promotes tumor necrosis in glioblastoma progression
(Nature Communications, 2020-12) Yee, Patricia P; Wei, Yiju; Kim, Soo-Yeon; Lu, Tong; Chih, Stephen Y; Lawson, Cynthia; Tang, Miaolu; Liu, Zhijun; Anderson, Benjamin; Thamburaj, Krishnamoorthy; Young, Megan M; Aregawi, Dawit G; Glantz, Michael J; Zacharia, Brad E; Specht, Charles S; Wang, Hong-Gang; Li, Wei
Abstract Tumor necrosis commonly exists and predicts poor prognoses in many cancers. Although it is thought to result from chronic ischemia, the underlying nature and mechanisms driving the involved cell death remain obscure. Here, we show that necrosis in glioblastoma (GBM) involves neutrophil-triggered ferroptosis. In a hyperactivated transcriptional coactivator with PDZ-binding motif-driven GBM mouse model, neutrophils coincide with necrosis temporally and spatially. Neutrophil depletion dampens necrosis. Neutrophils isolated from mouse brain tumors kill cocultured tumor cells. Mechanistically, neutrophils induce iron-dependent accumulation of lipid peroxides within tumor cells by transferring myeloperoxidase-containing granules into tumor cells. Inhibition or depletion of myeloperoxidase suppresses neutrophil-induced tumor cell cytotoxicity. Intratumoral glutathione peroxidase 4 overexpression or acyl-CoA synthetase long chain family member 4 depletion diminishes necrosis and aggressiveness of tumors. Furthermore, analyses of human GBMs support that neutrophils and ferroptosis are associated with necrosis and predict poor survival. Thus, our study identifies ferroptosis as the underlying nature of necrosis in GBMs and reveals a pro-tumorigenic role of ferroptosis. Together, we propose that certain tumor damage(s) occurring during early tumor progression (i.e. ischemia) recruits neutrophils to the site of tissue damage and thereby results in a positive feedback loop, amplifying GBM necrosis development to its fullest extent.