TIP30 loss enhances cytoplasmic and nuclear EGFR signaling and promotes lung adenocarcinogenesis in mice

Li, Aimin; Zhang, Chengliang; Gao, Shu‐Qin; Chen, Fengsheng; Yang, Chengfen; Luo, Rong; Xiao, Hua

doi:10.1038/onc.2012.253

Cited by 38 publications

(57 citation statements)

References 40 publications

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“…Both LN(AI) and LN95 cells are derived from LNCaP cells, but have been cultured under long-term ADT conditions, thus possessing an ADT-resistant phenotype. Using an absolute quantification method, real-time qPCR showed that VCaP cells expressed AR RNA that was 5-10 fold higher than LNCaP and LNCaP derived cells (Fig.1 and Suppl.1A), consistent with the report that VCaP cells have an increased AR gene copy number (35). AR RNA level was ~17.9 fold higher than AR-V7 in VCaP cells.…”

Section: Resultssupporting

confidence: 88%

Mechanisms of the androgen receptor splicing in prostate cancer cells

et al. 2013

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Prostate tumors develop resistance to androgen deprivation therapy (ADT) by multiple mechanisms, one of which is to express constitutively active androgen receptor (AR) splice variants lacking the ligand binding domain. AR splice variant 7 (AR-V7, also termed AR3) is the most abundantly expressed variant that drives prostate tumor progression under ADT conditions. However, the molecular mechanism by which AR-V7 is generated remains unclear. In this manuscript, we demonstrated that RNA splicing of AR-V7 in response to ADT was closely associated with AR gene transcription initiation and elongation rates. Enhanced AR gene transcription by ADT provides a pre-requisite condition that further increases the interactions between AR pre-mRNA and splicing factors. Under ADT conditions, recruitment of several RNA splicing factors to the 3’ splicing site for AR-V7 was increased. We identified two RNA splicing enhancers and their binding proteins (U2AF65 and ASF/SF2) that played critical roles in splicing AR pre-mRNA into AR-V7. These data indicate that ADT-induced AR gene transcription rate and splicing factor recruitment to AR pre-mRNA contribute to the enhanced AR-V7 levels in prostate cancer cells.

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Section: Resultssupporting

confidence: 88%

Mechanisms of the androgen receptor splicing in prostate cancer cells

et al. 2013

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“…We have previously demonstrated that the expression level of cyclin D1 was significantly increased in a mouse TIP30 knock-out model [18]. In our current study, we used qRT-PCR to confirm that TIP30 regulates cyclin D1 transcription.…”

Section: Tip30 Knockdown Upregulates Cyclin D1 Mrna Expression and Cesupporting

confidence: 57%

“…Our previous study showed that lung adenomas and adenocarcinomas developed spontaneously in Tip30 knock-out mice, and that the loss of TIP30 function caused the upregulation of EGFR downstream signaling targets in pulmonary cells, including EGFR, p-Akt, and p-Erk1/2. We also showed that TIP30 knockdown in human lung adenocarcinoma cells delayed EGFR degradation, and increased EGFR nuclear localization [18]. These findings suggest that EGF/EGFR signaling pathways may be involved in the role of TIP30 in lung adenocarcinomas.…”

mentioning

confidence: 78%

“…Extracellular stimuli, such as EGF stimulation, have been shown to induce sequential activation of Ras-MEK-ERK cascade to augment CCND1 transcription [22]. We previously reported that the number of cyclin D1-positive cells in lung tumors of TIP30 knock-out mice was higher than that in lung tumors in mice with functional TIP30 [18]. Thus, we speculated that TIP30 might also be involved in EGF-dependent cyclin D1 transcription.…”

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confidence: 91%

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TIP30 nuclear translocation negatively regulates EGF-dependent cyclin D1 transcription in human lung adenocarcinoma

et al. 2014

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“…Previous studies have demonstrated that the nuclear import of EGFR and the signal cascade induced by nuclear EGFR had pivotal roles in the malignant proliferation and survival of certain types of tumor tissues (35)(36)(37). Immunohistochemical analysis of breast tumor tissues revealed that EGFR expression levels in the nucleus are positively correlated with the expression of Ki-67, a biomarker of cell proliferation, and negatively correlated with the survival rate (38,39).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol mediates cell cycle arrest and cell death in human esophageal squamous cell carcinoma by directly targeting the EGFR signaling pathway

Jin

Feng

et al. 2016

Oncology Letters

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Abstract.Resveratrol is a small polyphenol that has been intensively studied in a wide spectrum of therapeutic fields. More recently, resveratrol has been demonstrated to exert its antitumor activity in numerous tumor models. The present study reported that resveratrol exhibited a marked anti-proliferative effect on human esophageal squamous cell carcinoma (ESCC) cells by inducing cell cycle G 0 /G 1 phase arrest and cell death, which was associated with a decrease in the expression levels of cyclin D1 and an increase in cleaved PARP/cleaved caspase-3 expression levels. The mechanisms underlying the antitumor potency of resveratrol were principally attributed to the downregulation of epidermal growth factor receptor (EGFR) signaling. The western blotting results showed that exposure of ESCC cells to resveratrol inhibited EGF-induced EGFR activation in addition to decreasing the total protein levels of EGFR and membrane/nuclear localization. In summary, the results suggested that resveratrol, or an associated analog, may have a role in the management of human ESCC. IntroductionHuman esophageal squamous cell carcinoma (ESCC) is the 6th leading cause of cancer-associated mortality, and the 8th most common type of cancer worldwide (1). ESCC is the most common histology of esophageal cancers, and has a high incidence in China, South Africa, France and Italy (2). Epidemiological and etiological studies have previously demonstrated that certain environmental and genetic factors have crucial roles in esophageal carcinogenesis (3-7). Although there have been advances in the fields of surgery and chemotherapy, the prognosis for ESCC is typically poor as the majority of patients diagnosed are elderly and present with advanced-stage disease, rendering them unsuitable for curative resection and maintaining the five-year survival rate for ESCC at <15% (1). Therefore, improving the current understanding of the molecular mechanisms underlying ESCC pathogenesis and identifying effective therapeutic agents are required to facilitate the development of novel therapies for this disease.Resveratrol is present in red grapes, wine, nuts and common garden plants, and is one of the most intensively investigated of all the phytochemicals with putative beneficial effects on human health (8). The effects of resveratrol include anti-oxidant and anti-aging properties, improvement of insulin sensitivity and reduction of cardiovascular disease risk (9-11). Previous studies have also indicated that resveratrol is able to function as a chemo preventive and chemotherapeutic agent in certain types of human carcinomas, including those of the colorectum, skin, liver, lung, pancreas, breast and prostate (8,(12)(13)(14). Previous studies suggesting that a dietary pattern rich in resveratrol may reduce the risk of ESCC (15). However, the molecular mechanisms underlying resveratrol-induced antitumor effects have yet to be elucidated. A number of potential mechanisms have been suggested to be involved in resveratrol-induced cancer preventative effects, i...

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TIP30 loss enhances cytoplasmic and nuclear EGFR signaling and promotes lung adenocarcinogenesis in mice

Cited by 38 publications

References 40 publications

Mechanisms of the androgen receptor splicing in prostate cancer cells

Mechanisms of the androgen receptor splicing in prostate cancer cells

TIP30 nuclear translocation negatively regulates EGF-dependent cyclin D1 transcription in human lung adenocarcinoma

Resveratrol mediates cell cycle arrest and cell death in human esophageal squamous cell carcinoma by directly targeting the EGFR signaling pathway

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