Overexpression of p300 correlates with poor prognosis in patients with cutaneous squamous cell carcinoma

Chen, M.-K.; Cai, Mengli; Luo, Rong; Xiang, Tian; Liao, Quan; Zhang, X.-Y.; Han, Ju

doi:10.1111/bjd.13226

Cited by 36 publications

(30 citation statements)

References 36 publications

(72 reference statements)

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“…Several reports have demonstrated p300 overexpression in other cancers, including skin, liver, esophageal, nasopharyngeal, lung, breast, prostate and colorectal cancers, and have described the poorer prognoses of patients with tumors with higher p300 expression level than of patients with tumors that express less p300 [9–16]. However, there is no data regarding p300 expression in pancreatic cancer.…”

Section: Resultsmentioning

confidence: 99%

“…Accumulating evidence has suggested an association between p300 overexpression and worse long-term survival of patients with various types of cancer, including lung, liver, colorectal, breast and esophageal cancer [9–16]. As p300 is involved in diverse biological activities both in benign epithelial and cancerous cells, the mechanism by which the overexpressed p300 impairs treatment outcomes of patients with cancer is not yet clearly defined.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, p300 plays a critical role in DNA repair synthesis after DNA damage induced by ultraviolet or radiation [5, 6]. While p300 is considered to serve as a tumor suppressor gene that prevents carcinogenesis in normal epithelial cells [7, 8], p300 has often been observed to be overexpressed in various types of cancer and p300 overexpression in such cancers has been associated with worse patient outcomes [9–16]. The mechanisms by which p300 overexpression worsens cancer outcomes are unknown.…”

Section: Introductionmentioning

confidence: 99%

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P300 inhibition enhances gemcitabine-induced apoptosis of pancreatic cancer

2016

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The transcriptional cofactor p300 has histone acetyltransferase activity (HAT) and has been reported to participate in chromatin remodeling and DNA repair. We hypothesized that targeting p300 can enhance the cytotoxicity of gemcitabine, which induces pancreatic cancer cell apoptosis by damaging DNA. Expression of p300 was confirmed in pancreatic cancer cell lines and human pancreatic adenocarcinoma tissues by western blotting and immunohistochemistry. When pancreatic cancer cells were treated with gemcitabine, p300 was recruited to chromatin within 24 hours, indicating the role in response to DNA damage. When p300 was gene-silenced with siRNA, histone acetylation was substantially reduced and pancreatic cancer cells were sensitized to gemcitabine. The selective p300 HAT inhibitor C646 similarly decreased histone acetylation, increased gemcitabine-induced apoptosis and thus enhanced the cytotoxicity of gemcitabine on pancreatic cancer cells. These findings indicate that p300 contributes to chemo-resistance of pancreatic cancer against gemcitabine and suggest that p300 and its HAT activity may be a potential therapeutic target to improve outcomes in patients with pancreatic cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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P300 inhibition enhances gemcitabine-induced apoptosis of pancreatic cancer

2016

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“…In this context, loss of heterozygosity (LOH) at the p300 locus has been observed in numerous cancers, including hepatocellular, colorectal, oral, breast, ovarian, gastric carcinomas and glioblastomas [11]. Consistently, several studies have also shown that loss of p300 correlates with aggressive features and poor prognosis of hepatocellular carcinoma (HCC) [12, 13], breast cancer [14], cutaneous squamous cell carcinoma (SCC) [15] and nasopharyngeal carcinoma [16]. However, p300 is also found to be overexpressed in prostate cancer, where it regulates fatty acid synthase expression, lipid metabolism and prostate cancer growth [5, 17, 18].…”

Section: Lysine Acetyltransferases Families and Their Link To Cancermentioning

confidence: 99%

The multifaceted role of lysine acetylation in cancer: prognostic biomarker and therapeutic target

Martile¹,

Bufalo²,

Trisciuoglio³

2016

Oncotarget

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Lysine acetylation is a post-translational modification that regulates gene transcription by targeting histones as well as a variety of transcription factors in the nucleus. Recently, several reports have demonstrated that numerous cytosolic proteins are also acetylated and that this modification, affecting protein activity, localization and stability has profound consequences on their cellular functions. Interestingly, most non-histone proteins targeted by acetylation are relevant for tumorigenesis. In this review, we will analyze the functional implications of lysine acetylation in different cellular compartments, and will examine our current understanding of lysine acetyltransferases family, highlighting the biological role and prognostic value of these enzymes and their substrates in cancer. The latter part of the article will address challenges and current status of molecules targeting lysine acetyltransferase enzymes in cancer therapy.

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“…Overexpression of HATs is observed in a wide variety of cancers. p300 overexpression has been linked to poor prognosis and survival in tumors including breast cancer, non-small cell lung cancer and cutaneous squamous cell carcinoma (Xiao et al, 2011;Hou et al, 2012;Chen et al, 2014). Besides the direct involvement of HATs in the oncogenic fusion, p300/CBP were also shown to modulate the activity of other fusion proteins.…”

Section: Mutations In Histone Acetylating Enzymesmentioning

confidence: 99%