Yes-associated protein (YAP) functions as a tumor suppressor in breast

Abstract

Yes-associated protein (YAP) has been shown to positively regulate p53 family members and to be negatively regulated by the AKT proto-oncogene product in promoting apoptosis. On the basis of this function and its location at 11q22.2, a site of frequent loss of heterozygosity (LOH) in breast cancer, we investigated whether YAP is a tumor suppressor in breast. Examination of tumors by immunohistochemistry demonstrated significant loss of YAP protein. LOH analysis revealed that protein loss correlates with specific deletion of the YAP gene locus. Functionally, short hairpin RNA knockdown of YAP in breast cell lines suppressed anoikis, increased migration and invasiveness, inhibited the response to taxol and enhanced tumor growth in nude mice. This is the first report indicating YAP as a tumor suppressor, revealing its decreased expression in breast cancer as well as demonstrating the functional implications of YAP loss in several aspects of cancer signaling.

A temporal requirement for Hippo signaling in mammary gland differentiation, growth, and tumorigenesis

“…Consistent with an oncogenic function, YAP/TAZ can promote epithelial-to-mesenchymal transition (Overholtzer et al 2006;Chan et al 2008), metastasis Lamar et al 2012), and selfrenewal (Cordenonsi et al 2011) of breast cancer cells. Paradoxically, several studies have reported loss of YAP expression in human breast tumors as well as a correlation between improved patient survival and increased YAP mRNA levels, thereby implicating YAP as a breast cancer tumor suppressor (Matallanas et al 2007;Yuan et al 2008). Consistent with the latter view, it was shown that RNAi knockdown of YAP in breast cell lines suppressed anoikis, increased migration and invasiveness, and enhanced tumor growth in nude mice (Yuan et al 2008).…”

“…Paradoxically, several studies have reported loss of YAP expression in human breast tumors as well as a correlation between improved patient survival and increased YAP mRNA levels, thereby implicating YAP as a breast cancer tumor suppressor (Matallanas et al 2007;Yuan et al 2008). Consistent with the latter view, it was shown that RNAi knockdown of YAP in breast cell lines suppressed anoikis, increased migration and invasiveness, and enhanced tumor growth in nude mice (Yuan et al 2008). Reconciling these contrasting findings presents a challenge, especially given the heterogeneity of the genetic makeup of the tumor cells.…”

YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma through ZEB2-dependent DNp63 repression

“…YAP is frequently activated in various epithelial cancer types and considered as a rising star for cancer therapeutics 10 . Nonetheless, several other studies also implicate YAP as a tumour suppressor [44][45][46] , suggesting that YAP might have opposing functions in organ-and genetic-context-dependent manner. Our data have shown that YAP knockdown in A549 cells resulted in decreased cell proliferation and anchorageindependent cell growth in vitro (Supplementary Fig.…”

Expression of YAP in the Skin Lesions of Lichen Planus

“…In recent years, it was found to be upregulated in many tumors [10][11][12]. It may be through regulating cell proliferation; apoptosis, Epithelial Mesenchymal Transition (EMT), intercellular contact inhibition and self-renewal of stem cells that YAP participate in the occurrence and development of tumors [20][21][22][23][24], so it is considered as an oncogene. By immunohistochemical staining, researchers have found that YAP is upregulated in a wide variety of human cancers including liver cancer [25], breast cancer [26], lung cancer [27], gastric cancer, esophageal cancer [28] and colorectal cancer [29].…”