Mutant p53 regulates Survivin to foster lung metastasis

Tang, Qiaosi; Efe, Gizem; Chiarella, Anna M.; Leung, Jessica C.; Chen, Maoting; Yamazoe, Taiji; Su, Zhenyi; Pitarresi, Jason R.; Li, Jinyang; Islam, Mirazul; Karakasheva, Tatiana A.; Klein‐Szanto, Andres J.; Pan, Samuel; Hu, Jianhua; Natsugoe, Shoji; Gu, Wei; Stanger, Ben Z.; Wong, Kwok-K; Diehl, J. Alan; Bass, Adam J.; Nakagawa, Hiroshi; Murphy, Maureen E.; Rustgi, Anil K.

doi:10.1101/gad.340505.120

Cited by 19 publications

(10 citation statements)

References 48 publications

(58 reference statements)

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“…Interestingly, it has been shown that wild type of the tumor suppressor gene p53 could subdue Survivin expression [ 61 ], suggesting that non-functional p53 in cancer could result in higher Survivin expression. Similar conclusions were also determined in a recent study showing elevated Survivin expression in mice with p53-mutated esophageal squamous cell carcinoma, which could play a role in aiding lung metastasis [ 62 ]. A clinical study examined the genome and transcriptome of 198 lung squamous cell carcinomas and found that BIRC5 amplification was prevalent in tumors with p53 mutations [ 63 ].…”

Section: Discussionsupporting

confidence: 89%

Pan-cancer analysis identifies BIRC5 as a prognostic biomarker

et al. 2022

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Background The BIRC5 gene encodes for the Survivin protein, which is a member of the inhibitor of apoptosis family. Survivin is found in humans during fetal development, but generally not in adult cells thereafter. Previous studies have shown that Survivin is abundant in most cancer cells, thereby making it a promising target for anti-cancer drugs and a potential prognostic tool. Methods To assess genetic alterations and mutations in the BIRC5 gene as well as BIRC5 co-expression with other genes, genomic and transcriptomic data were downloaded via cBioPortal for approximately 9000 samples from The Cancer Genome Atlas (TCGA) representing 33 different cancer types and 11 pan-cancer organ systems, and validated using the ICGC Data Portal and COSMIC. TCGA BIRC5 RNA sequencing data from 33 different cancer types and matching normal tissue samples for 16 cancer types were downloaded from Broad GDAC Firehose and validated using breast cancer microarray data from our previous work and data sets from the GENT2 web-based tool. Survival data were analyzed with multivariable Cox proportional hazards regression analysis and validated using KM plotter for breast-, ovarian-, lung- and gastric cancer. Results Although genetic alterations in BIRC5 were not common in cancer, BIRC5 expression was significantly higher in cancer tissue compared to normal tissue in the 16 different cancer types. For 14/33 cancer types, higher BIRC5 expression was linked to worse overall survival (OS, 4/14 after adjusting for both age and tumor grade and 10/14 after adjusting only for age). Interestingly, higher BIRC5 expression was associated with better OS in lung squamous cell carcinoma and ovarian serous cystadenocarcinoma. Higher BIRC5 expression was also linked to shorter progressive-free interval (PFI) for 14/33 cancer types (4/14 after adjusting for both age and tumor grade and 10/14 after adjusting only for age). External validation showed that high BIRC5 expression was significantly associated with worse OS for breast-, lung-, and gastric cancer. Conclusions Our findings suggest that BIRC5 overexpression is associated with the initiation and progression of several cancer types, and thereby a promising prognostic biomarker.

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Section: Discussionsupporting

confidence: 89%

Pan-cancer analysis identifies BIRC5 as a prognostic biomarker

et al. 2022

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“…While we still must do IHC on exactly the same silicone nitride widows scanned by XFM in order to provide the final confirmation that nanocomposites colocalize with BIRC5, imaging of single cells analogous to work shown in Figure 4 may provide us with additional proofs for this possibility. BIRC5 plays numerous roles in carcinogenesis and metastasis, and has therefore been targeted by different small molecule, antibody, and nanocomposite therapies, both on its own or through its binding with Hsp90 [54,56,[62][63][64][65][66][67][68][69]. In this work, we found that non-targeted dopamine-coated Fe 3 O 4 @TiO 2 nanocomposites have a high affinity for BIRC5, making it one of the proteins of the "hard" protein corona.…”

Section: Discussionmentioning

confidence: 72%

Development of Multi-Scale X-ray Fluorescence Tomography for Examination of Nanocomposite-Treated Biological Samples

Chen

Lastra

Paunesku

et al. 2021

Cancers

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Research in cancer nanotechnology is entering its third decade, and the need to study interactions between nanomaterials and cells remains urgent. Heterogeneity of nanoparticle uptake by different cells and subcellular compartments represent the greatest obstacles to a full understanding of the entire spectrum of nanomaterials’ effects. In this work, we used flow cytometry to evaluate changes in cell cycle associated with non-targeted nanocomposite uptake by individual cells and cell populations. Analogous single cell and cell population changes in nanocomposite uptake were explored by X-ray fluorescence microscopy (XFM). Very few nanoparticles are visible by optical imaging without labeling, but labeling increases nanoparticle complexity and the risk of modified cellular uptake. XFM can be used to evaluate heterogeneity of nanocomposite uptake by directly imaging the metal atoms present in the metal-oxide nanocomposites under investigation. While XFM mapping has been performed iteratively in 2D with the same sample at different resolutions, this study is the first example of serial tomographic imaging at two different resolutions. A cluster of cells exposed to non-targeted nanocomposites was imaged with a micron-sized beam in 3D. Next, the sample was sectioned for immunohistochemistry as well as a high resolution “zoomed in” X-ray fluorescence (XRF) tomography with 80 nm beam spot size. Multiscale XRF tomography will revolutionize our ability to explore cell-to-cell differences in nanomaterial uptake.

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“…Recent studies indicate that overexpression of survivin enhanced angiogenesis and metastasis. Pharmaceutical inhibition of survivin, or reduction of survivin protein level, suppressed metastasis of breast 25 , ovarian 26 , and lung cancer 27 . Moreover, the high protein level of survivin is corrected with the poor prognosis of HNSCC and NPC [28][29][30] .…”

Section: Discussionmentioning

confidence: 98%

“…The natural product Butein is a potent anti-tumor agent against human malignancies 17 , 18 . Previous studies have shown that Butein suppresses osteosarcoma 19 , cervical cancer 20 , 21 , colorectal cancer 22 , hepatocellular carcinoma 23 , breast cancer 24 , 25 , lung cancer 26 , and oral squamous cell carcinoma 27 . The mechanism studies have identified multiple intracellular targets of Butein, including AurkB, mTOR, NF-κB, EGFR, and c-Met 17 , 28 – 30 .…”

Section: Introductionmentioning

confidence: 99%

Butein promotes ubiquitination-mediated survivin degradation inhibits tumor growth and overcomes chemoresistance

Dong

Liu

et al. 2022

Sci Rep

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Overexpression of survivin is frequently observed in human malignancies and is associated with poor prognosis. The present study found that survivin is highly expressed in nasopharyngeal carcinoma (NPC) tumor tissues. Depleting survivin with shRNA inhibited cell viability, colony formation, and in vivo tumorigenesis of NPC cells. With a natural product screening, we identified Butein as a potential anti-tumor compound for NPC by reducing survivin protein level. Butein shortened the half-life of survivin and enhanced ubiquitination-mediated degradation. The mechanism study showed that Butein promoted the interaction between survivin and E3 ligase Fbxl7, and the knockdown of Fbxl7 compromised Butein-induced survivin ubiquitination. Butein suppressed the Akt-Wee1-CDK1 signaling and decreased survivin Thr34 phosphorylation, facilitating E3 ligase Fbxl7-mediated survivin ubiquitination and degradation. Moreover, Butein exhibited a strong in vivo anti-tumor activity, as the tumor volume of Butein-treated xenografts was reduced significantly. Butein alone or combined with cisplatin (CDDP) overcame chemoresistance in NPC xenograft tumors. Overall, our data indicate that Butein is a promising anti-tumor agent for NPC treatment.

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Mutant p53 regulates Survivin to foster lung metastasis

Abstract: 340505.120. Freely available online through the Genes & Development Open Access option.

Cited by 19 publications

References 48 publications

Pan-cancer analysis identifies BIRC5 as a prognostic biomarker

Pan-cancer analysis identifies BIRC5 as a prognostic biomarker

Development of Multi-Scale X-ray Fluorescence Tomography for Examination of Nanocomposite-Treated Biological Samples

Butein promotes ubiquitination-mediated survivin degradation inhibits tumor growth and overcomes chemoresistance

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