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Parnian Ahmadi Moghaddam, Kristine M Cornejo, Lloyd Hutchinson, Keith Tomaszewicz, Karen Dresser, April Deng, Patrick OʼDonnell
Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine tumor that typically occurs on the head and neck of the elderly and follows an aggressive clinical course. Merkel cell polyomavirus (MCPyV) has been identified in up to 80% of cases and has been shown to participate in MCC tumorigenesis. Complete spontaneous regression of MCC has been rarely reported in the literature. We describe a case of a 79-year-old man that presented with a rapidly growing, 3-cm mass on the left jaw. An incisional biopsy revealed MCC...
October 12, 2016: American Journal of Dermatopathology
Raffaella Sordella, Nitin H Shirole, Debjani Pal, Edward R Kastenhuber, Serif Senturk, Joseph Boroda, Paola Pisterzi, Madison Miller, Gustavo Munoz, Marko Anderluh, Marc Ladanyi, Scott W Lowe
TP53 truncating mutations are common in human tumors and are thought to give rise to p53-null alleles. Here, we show that TP53 exon-6 truncating mutations occur at higher than expected frequencies and produce proteins that lack canonical p53 tumor suppressor activities but promote cancer cell proliferation, survival, and metastasis. Functionally and molecularly, these p53 mutants resemble the naturally occurring alternative p53 splice variant, p53-psi. Accordingly, these mutants can localize to mitochondria where they promote tumor phenotypes by binding and activating the mitochondria inner pore permeability regulator, Cyclophilin D (CypD)...
October 19, 2016: ELife
Zhen-Yao Chen, Xin Chen, Zhao-Xia Wang
MicroRNAs are a large group of non-coding RNAs that have emerged as regulators of various biological processes, especially carcinogenesis and cancer progression. Recent evidence has shown that microRNA-196a (miR-196a) is upregulated in most types of tumors and involved in multiple biological processes via translational inhibition and mRNA cleavage, such as cell proliferation, migration, and invasion, mostly functioning as an oncogene. Dysregulation of miR-196a promotes oncogenesis and tumor progression. In this review, we summarize the upstream regulators, target genes, signaling pathways, and single nucleotide polymorphisms of miR-196a, which collectively affect cell proliferation, migration, and invasion...
October 18, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Qingqing Liu, Tao Tao, Fang Liu, Runzhou Ni, Cuihua Lu, Aiguo Shen
As an essential post-translational modification, O-GlcNAcylation has been thought to be able to modulate various nuclear and cytoplasmic proteins and is emerging as a key regulator of multiple biological processes, such as transcription, cell growth, signal transduction, and cell motility. Recently, authoritative glycomics analyses have reported extensive crosstalk between O-GlcNAcylation and phosphorylation, which always dynamically interplay with each other and regulate signaling, transcription, and other cellular processes...
October 14, 2016: Experimental Cell Research
Wensheng Zhang, Erik K Flemington, Kun Zhang
Most cancers are driven by somatic mutations in proto-oncogenes and tumor suppressor genes. Genetic changes in a tumor may accumulate in the tissue self-renewal phase prior to neoplasm. The risk of sporadic mutations increases with age. In this regard, a positive association between patient age and the accumulated mutation burden in tumors exists for many cancer types. However, the reported lines of evidence for such a connection are still limited. TP53 is the most frequently mutated cancer gene. The encoded p53 protein plays crucial roles in DNA repair...
September 2016: Cancer Genetics
Jinhyun Cho, Jeeyun Lee, Jusun Kim, Seung Tae Kim, Sujin Lee, Sun Young Kim, Sang Yun Ha, Cheol-Keun Park, Ho Yeong Lim
BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death globally. Mechanistic target of rapamycin (mTOR) is frequently up-regulated in HCC and plays an important role in HCC tumorigenesis. Tumors with loss of tuberous sclerosis complex 2 (TSC2), a negative regulator of mTOR signaling, tend to respond well to mTOR inhibitors. We analyzed TSC2 expression status in Korean patients with HCC and evaluated the correlation between TSC2 loss and response to the mTOR inhibitor, everolimus...
October 2016: Translational Oncology
Logan Horne, Frank R Avilucea, Huifeng Jin, Jared J Barrott, Kyllie Smith-Fry, Yanliang Wang, Bang H Hoang, Kevin B Jones
Previous reports document expression of low-density lipoprotein receptor-related protein 5 (LRP5) in osteosarcoma (OS) tissue. Expression of this Wnt receptor correlated with metastatic disease and poor disease-free survival. Forced expression of dominant-negative LRP5 (dnLRP5), which lacks the membrane binding domain of the native protein and therefore functions as a soluble receptor-sponge for Wnt ligands, reduced in vitro cellular invasion and in vivo xenograft tumor growth for osteosarcoma cell lines. Here, we use a genetically engineered mouse model of osteosarcomagenesis with and without expression of dnLRP5 to assess to what degree tumorigenesis is affected and whether Wnt/β-catenin signaling is circumvented or maintained...
October 2016: Translational Oncology
Nicole E McNeil, Hesed M Padilla-Nash, Floryne O Buishand, Yue Hue, Thomas Ried
Human colorectal carcinomas are defined by a non-random distribution of genomic imbalances that are characteristic for this disease. Often, these imbalances affect entire chromosomes. Understanding the role of these aneuploidies for carcinogenesis is of utmost importance. Currently, established transgenic mice do not recapitulate the pathognonomic genome aberration profile of human colorectal carcinomas. We have developed a novel model based on the spontaneous transformation of murine colon epithelial cells...
October 17, 2016: Genes, Chromosomes & Cancer
Jing Hu, Jie Liu, Aozheng Chen, Jia Lyu, Guihai Ai, Qiongjing Zeng, Yi Sun, Chunxia Chen, Jinbo Wang, Jin Qiu, Yi Wu, Jiajing Cheng, Xiujuan Shi, Liwen Song
Ino80 ATPase is an integral component of the INO80 ATP-dependent chromatin-remodeling complex, which regulates transcription, DNA repair and replication. We found that Ino80 was highly expressed in cervical cancer cell lines and tumor samples. Ino80 knockdown inhibited cervical cancer cell proliferation, induced G0/G1 phase cell cycle arrest in vitro and suppressed tumor growth in vivo. However, Ino80 knockdown did not affect cell apoptosis, migration or invasion in vitro. Ino80 overexpression promoted proliferation in the H8 immortalized cervical epithelial cell line, which has low endogenous Ino80 expression as compared to cervical cancer cell lines...
October 14, 2016: Oncotarget
Lan He, Priscilla T Y Law, Siaw Shi Boon, Chuqing Zhang, Wendy C S Ho, Lawrence Banks, C K Wong, Juliana C N Chan, Paul K S Chan
Epidemiological evidence supports that infection with high-risk types of human papillomavirus (HPV) can interact with host and environmental risk factors to contribute to the development of cervical, oropharyngeal, and other anogenital cancers. In this study, we established a mouse epithelial cancer cell line, designated as Chinese University Papillomavirus-1 (CUP-1), from C57BL/KsJ mice through persistent expression of HPV-16 E7 oncogene. After continuous culturing of up to 200 days with over 60 passages, we showed that CUP-1 became an immortalized and transformed epithelial cell line with continuous E7 expression and persistent reduction of retinoblastoma protein (a known target of E7)...
2016: PloS One
Jia-Jie Hao, De-Chen Lin, Huy Q Dinh, Anand Mayakonda, Yan-Yi Jiang, Chen Chang, Ye Jiang, Chen-Chen Lu, Zhi-Zhou Shi, Xin Xu, Yu Zhang, Yan Cai, Jin-Wu Wang, Qi-Min Zhan, Wen-Qiang Wei, Benjamin P Berman, Ming-Rong Wang, H Phillip Koeffler
Esophageal squamous cell carcinoma (ESCC) is among the most common malignancies, but little is known about its spatial intratumoral heterogeneity (ITH) and temporal clonal evolutionary processes. To address this, we performed multiregion whole-exome sequencing on 51 tumor regions from 13 ESCC cases and multiregion global methylation profiling for 3 of these 13 cases. We found an average of 35.8% heterogeneous somatic mutations with strong evidence of ITH. Half of the driver mutations located on the branches of tumor phylogenetic trees targeted oncogenes, including PIK3CA, NFE2L2 and MTOR, among others...
October 17, 2016: Nature Genetics
Lin Xu, Zhu Wang, Shan-Yang He, Su-Fen Zhang, Hong-Jiao Luo, Kai Zhou, Xiao-Fei Li, Shao-Peng Qiu, Kai-Yuan Cao
Prostate cancer (PCa) is one of the most common malignant tumors and the second leading cause of cancer-related death among males. Bax-interacting factor-1 (Bif-1) is a member of Endophilin family, which binds to and activates the BAX protein in response to the apoptosis signaling pathway. Loss of Bif-1 may suppress the intrinsic pathway of apoptosis and promote tumorigenesis, but there is also converse evidence that Bif-1 could in part be responsible for the tumorigenesis and the role of Bif-1 in PCa development is not clear...
October 14, 2016: Oncology Reports
Yali Chen, Qianxiang Zhou, Lei Zhang, Ran Wang, Meihua Jin, Yuling Qiu, Dexin Kong
Increasing resistance of imatinib, a BCR-ABL tyrosine kinase inhibitor, hinders its use in the therapy of chronic myeloid leukemia (CML). The PI3K pathway is known to be closely involved in BCR-ABL transformation and the tumorigenesis of CML, suggesting that PI3K may be a potential target for CML therapy. Idelalisib, a specific inhibitor of PI3K p110δ, has been approved for the treatment of chronic lymphocytic leukemia (CLL). However, the antileukemia effect of idelalisib on CML remains unknown. In the present study, the antileukemia activity of idelalisib alone or in combination with imatinib was investigated by use of K562 cells...
October 17, 2016: Oncology Reports
Ying Liu, Lijun Miao, Ran Ni, Hui Zhang, Ling Li, Xinhua Wang, Xin Li, Jing Wang
Formation of cancer stem cells (CSCs) and increased cells proliferation are involved in tumorigenesis, tumour recurrence and therapy resistance and microRNA is essential for the development of the biological traits of CSCs and the increased cells proliferation. Studying molecular mechanism of tumorigenesis, tumour recurrence and therapy resistance of lung cancer will help us to further understand the pathogenesis and progression of the disease and offer new targets for effective therapies. In the present study, we found that miR-520a-3p expression is downregulated in NSCLC (non-small cell lung cancer) and SCLC (small cell lung cancer)...
October 5, 2016: Oncology Reports
Yanke Chen, Xiaofei Wang, Jiwen Cheng, Zhen Wang, Ting Jiang, Ni Hou, Na Liu, Tusheng Song, Chen Huang
Growing evidence indicates that some abnormally expressed microRNAs (miRNAs) influence tumorigenesis and progression. Previous studies reported that miR-20a is among the frequently altered miRNAs in human hepatocellular carcinoma (HCC), but its expression pattern and role in HCC remain controversial. In the present study, we demonstrated that miR-20a-5p exhibited aberrant expression in HCC tissues compared with paired non-tumor tissues: 52% of the tumor samples showed a greater increase. Overexpression of miR-20a contributed to HCC cell proliferation and migration in vitro, and treatment with anti-miR20a-5p caused the opposite effects...
October 4, 2016: Oncology Reports
Ruiling Wen, Yingying Xiao, Yuhua Zhang, Min Yang, Yongping Lin, Jun Tang
Tubulin tyrosine ligase like 12 (TTLL12), a member of the tubulin tyrosine ligase (TTLL) family, has not been completely characterized to date. It is reported that histone methylation, tubulin modifications, mitotic duration and chromosome ploidy play crucial roles in a variety of cancers, and are related to tumorigenesis and cancer progression. A recent study showed that TTLL12 may be a pseudo-enzyme which has a SET-like domain and a TTL-like domain. In the present study, we first used 3'-rapid amplification of cDNA ends (3'-RACE) to amplify the transcripts of the TTLL12 gene from a human lung cancer cell line H1299, and unexpectedly discovered a new transcript isoform characterized with an additional 108-bp nucleotide sequence inserted at the location from 902 to 903 bases of the TTLL12 coding sequence (CDS), where it also locates between exons 5 and 6...
September 28, 2016: Oncology Reports
Zhijie Dai, Jun Wu, Fenghua Chen, Quan Cheng, Mingyu Zhang, Ying Wang, Yong Guo, Tao Song
CXCL5 and its receptor CXCR2 have been found to be involved in tumorigenesis and cancer progression. Recent studies have shown that CXCR2 is upregulated in glioma tissues, and associated with poor prognosis and recurrence. However, the role of CXCL5/CXCR2 signaling in mediating the malignant phenotypes of glioma cells, as well as the underlying mechanism, still remains unclear. In the present study, we found that CXCL5 was upregulated in glioma tissues compared to that noted in normal brain tissues. High CXCL5 levels were significantly associated with higher tumor grade, advanced clinical stage, and shorter survival time of glioma patients...
October 10, 2016: Oncology Reports
Fa-Min Zeng, Yang-Min Xie, Lian-Di Liao, Li-Yan Li, Bo Chen, Jian-Jun Xie, Li-Yan Xu, En-Min Li
The key molecular events that contribute to tumorigenesis are incompletely understood. The aim of the present study was to characterize and compare the biological phenotypes of three human telomerase reverse transcriptase (hTERT) and/or human papillomavirus 16 E6 and E7‑immortalized esophageal epithelial cell lines, NE2‑hTERT (NE2), NE3‑E6E7‑hTERT (NE3) and NEcA6‑E6E7‑hTERT (NEcA6). The present study used soft‑agar colony formation assays, tumorigenicity assays in nude mice, and cell proliferation, adhesion and migration assays to identify the biological characteristics of NE2, NE3 and NEcA6 cells...
October 6, 2016: Molecular Medicine Reports
L A Jung, A Gebhardt, W Koelmel, C P Ade, S Walz, J Kuper, B von Eyss, S Letschert, C Redel, L d'Artista, A Biankin, L Zender, M Sauer, E Wolf, G Evan, C Kisker, M Eilers
MYC genes have both essential roles during normal development and exert oncogenic functions during tumorigenesis. Expression of a dominant-negative allele of MYC, termed OmoMYC, can induce rapid tumor regression in mouse models with little toxicity for normal tissues. How OmoMYC discriminates between physiological and oncogenic functions of MYC is unclear. We have solved the crystal structure of OmoMYC and show that it forms a stable homodimer and as such recognizes DNA in the same manner as the MYC/MAX heterodimer...
October 17, 2016: Oncogene
D-L Qi, D Cobrinik
Retinoblastomas can arise from cone photoreceptor precursors in response to the loss of pRB function. Cone precursor-specific circuitry cooperates with pRB loss to initiate this process and subsequently contributes to the malignancy. Intrinsic high-level MDM2 expression is a key component of the cone precursor circuitry and is thought to inactivate p53-mediated tumor surveillance, which could otherwise be induced in response to pRB loss. However, the MDM2-related MDM4 has also been proposed to abrogate p53-mediated tumor surveillance in the absence of detectable MDM2 in retinoblastoma cells, bringing into question the importance of high-level MDM2 versus MDM4 expression...
October 17, 2016: Oncogene
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