YAP promotes self-renewal of gastric cancer cells by inhibiting expression of L-PTGDS and PTGDR2
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
Authors: Bie, Qingli; Li, Xiaozhe; Liu, Shiqi; Yang, Xiao; Qian, Zhenwen; Zhao, Rou; Zhang, Xiaobei; Zhang, Bin
Abstract
Introduction Cancer stem cells have been implicated angiogenesis of tumor and invasiveness, drug resistance in tumors. Yes-associated protein 1 (YAP) owns carcinogenic roles in various organs, but the role of YAP in cancer stem cells of gastric cancer (GC) remains unclear. In this study, we explored the function and mechanism of YAP in GC cancer stem cells. Materials and methods, and results First, we confirmed that the expression of YAP mRNA and protein in GC tissues was higher than in adjacent tissues by RT-PCR, western blot and immunohistochemistry. Immunofluorescence staining of the GC tissues revealed that the region of YAP expression coincided with the region of expression of the cancer stem cell marker SALL4 but did not overlap with that of the epithelial marker cytokeratin 14 (CK14). Additional research revealed that spherical cells expressed relatively high levels of YAP protein, and YAP overexpression reinforced self-renewal and expression of stem cell markers in the GC cells. Knockdown the expression of YAP reversed this phenomenon. Second, we examined the expression patterns of lipocalin-type prostaglandin D2 synthase (L-PTGDS) and prostaglandin D2 receptor 2 (PTGDR2) in GC tissues and proved that there was negatively correlation between the expression of L-PTGDS and PTGDR2 and YAP in GC tissues. Finally, we confirmed that YAP inhibited the expression of L-PTGDS and PTGDR2 by gain- and loss-of-function experiments. Moreover, the overexpression of L-PTGDS and PTGDR2 suppressed the proliferation and self-renewal induced by YAP in vitro and reversed the pro-tumor effect of YAP in vivo. Conclusion Our results revealed a novel function of YAP and the mechanism underlying cancer stem cell regulation by YAP.
A Case of Carcinosarcoma of the Breast Presenting as Inflammatory Carcinoma and Review of the Literature
CUREUS
Authors: Lakshmi, Harish Neelamraju; Saini, Devendra; Om, Prabha; Verma, Naveen
Abstract
Carcinosarcoma, also known as metaplastic carcinoma, is a rare and aggressive malignant tumor. We report a case of metaplastic carcinoma presenting as inflammatory carcinoma and provide a review of the related literature. A 38-year-old breastfeeding woman presented with concerns about a painful lump in her left breast. The symptoms had been present for two months. After admission to the hospital, the triple assessment revealed findings consistent with inflammatory carcinoma of the breast. The patient underwent modified radical mastectomy. Histopathological examination revealed a gray-white tumor with a biphasic pattern with features of ductal carcinoma as well as squamous and sarcomatous differentiation. On immunohistochemistry, the neoplastic cells were positive for cytokeratin and vimentin, and focally positive for smooth muscle antigen (SMA) and negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER-2/neu). Based on histological and immunohistochemical findings, the tumor was diagnosed as carcinosarcoma. Four of eighteen dissected axillary lymph nodes were positive for metastasis. Carcinosarcoma is often a triple-negative tumor. The lack of standardized treatment protocols frequently leads to poor prognosis and can pose a diagnostic dilemma; it should be part of the differential diagnosis for a case of carcinoma of the breast presenting as inflammatory carcinoma.