Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer

Abstract

BackgroundYes Associated Protein (YAP) has been implicated in the control of organ size by regulating cell proliferation and survival. YAP is a transcriptional coactivator that controls cellular responses through interaction with TEAD transcription factors in the nucleus, while its transcriptional functions are inhibited by phosphorylation-dependent translocation to the cytosol. YAP overexpression has been associated with different types of cancer, such as lung, skin, prostate, ovary and liver cancer. Recently, YAP was linked to E-cadherin-dependent regulation of contact inhibition in breast cancer cells.ResultsIn this study we examined YAP protein expression and cellular localization in 237 cases of human invasive breast cancer by immunohistochemistry and related its expression to clinicopathological features and E-cadherin expression. We observed that invasive lobular carcinoma is characterized by higher expression levels of both nuclear and cytosolic YAP (p < 0.001). Nuclear YAP expression did not associate with other variables such as lymph node involvement, tumor grade, tumor size, mitotic activity or the molecular sub-types of invasive breast cancer. We observed that high nuclear and cytosolic YAP expression are associated with the E-cadherin deficient breast cancer subtype ILC (p < 0.001) and cell lines derived from human breast cancers and conditional mouse models of human lobular breast cancer.ConclusionsSince our data indicate that nuclear YAP localization is more common in breast cancers lacking functional adherens junctions, it suggests that YAP-mediated transcription may be involved in the development and progression of invasive lobular breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1007/s13402-013-0143-7) contains supplementary material, which is available to authorized users.

Expression of YAP in the Skin Lesions of Lichen Planus

“…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]. YAP was also found to be correlated with some skin and mucosa tumors, such as oral squamous cell carcinoma [30], malignant melanoma [31,32] and head and neck cancers [33].…”

The Hippo pathway in colorectal cancer

“…The most commonly focused gene, YAP1, was found to be involved in tumour development and progression in different malignancies, including CRC. Although increased level of the YAP1 protein (assessed by WB) was found in most studies [83,[88][89][90][91] suggesting its oncogenic role, the under-expression was also observed in breast [92] and colorectal cancer [79]. The study of Barry et al showed decreased expression of YAP1 in high grade tumours and stage IV [79].…”

“…Mouse KO: various cancer types developed [141] TSG: downregulation in CRC [142] TAZ Mutations in Barth syndrome [143] OG: overexpression in breast cancer [144], HCC [145] OG: overexpression in CRC [85] YAP1 OG: overexpression in NSCLC [88], prostate [90], breast [91], gallbladder cancer [146] and glioma [89] TSG: decreased expression in breast cancer [92] OG: overexpression in CRC [83], in CRC cases resistant to cetuximab [102] TSG: underexpression in CRC [79] AML -acute myeloid leukaemia; CCL -cancer cell line(s); HCC -hepatocellular carcinoma; KO -knock out; LOH -loss of heterozygosity; NSCLC -non-small cell lung cancer; OG -oncogene; TSG -tumour suppressor gene epinephrine or glucagon repress YAP1/TAZ activity [45,46]. YAP1 could also be regulated by matrix stiffness independently from LATS1/2 phosphorylation.…”

The Transcriptional Regulators TAZ and YAP Direct Transforming Growth Factor β-induced Tumorigenic Phenotypes in Breast Cancer Cells

“…For instance, the extent of nuclear TAZ or YAP levels corresponds with breast cancer tumor grade (2)(3)(4). In breast cancer cells, enhanced nuclear TAZ and YAP levels promote oncogenic transformation and endow cells with tumorigenic properties, including the ability to proliferate, subvert apoptotic cues, migrate, invade, and grow under anchorage-independent conditions (5-9).…”