Polo-like kinase 1 inhibitor BI 6727 induces DNA damage and exerts strong antitumor activity in small cell lung cancer
The prognosis of small cell lung cancer (SCLC) is poor despite its good initial response to chemotherapy. Polo-like kinase 1 (PLK1) is a crucial mitotic regulator that is overexpressed in many tumors, and its overexpression is associated with tumor aggressiveness and a poor prognosis. However, its role in SCLC is still poorly characterized. Based on immunohistochemistry findings, the PLK1 protein is expressed at higher levels in SCLC tumor samples than in normal lung tissue samples. The selective PLK1 inhibitor BI 6727 significantly induced the inhibition of proliferation and apoptosis in a dose-dependent manner in SCLC ce...
Source: Cancer Letters - August 14, 2018 Category: Cancer & Oncology Authors: Yuehong Wang, Linying Wu, Yinan Yao, Guohua Lu, Liming Xu, Jianying Zhou Tags: Original Articles Source Type: research
Designer hydrogels: Shedding light on the physical chemistry of the pancreatic cancer microenvironment
Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer mortality in the United States, with a 5-year survival of ∼8%. PDAC is characterized by a dense and hypo-vascularized stroma consisting of proliferating cancer cells, cancer-associated fibroblasts, macrophages and immune cells, as well as excess matrices including collagens, fibronectin, and hyaluronic acid. In addition, PDAC has increased interstitial p ressures and a hypoxic/acidic tumor microenvironment (TME) that impedes drug delivery and blocks cancer-directed immune mechanisms. (Source: Cancer Letters)
Source: Cancer Letters - August 14, 2018 Category: Cancer & Oncology Authors: Chien-Chi Lin, Murray Korc Tags: Mini-review Source Type: research
TGF- β-induced STAT3 overexpression promotes human head and neck squamous cell carcinoma invasion and metastasis through malat1/miR-30a interactions
Aberrant signal transducer and activator of transcription 3 (STAT3) signaling is a critical factor that drives the invasion and metastasis of head and neck squamous cell carcinoma (HNSCC). However, the underlying mechanisms of STAT3 overexpression and regulation of HNSCC metastasis remain unknown. In the current study, we demonstrated that upregulated TGF- β may promote epithelial-mesenchymal transition (EMT) through STAT3 activation. In addition, we explored the contributions of STAT3 to HNSCC with a specific focus on its transcriptional regulation and its interaction with the long noncoding RNA (lncRNA) metastasis assoc...
Source: Cancer Letters - August 14, 2018 Category: Cancer & Oncology Authors: Yu Wang, Chuanqiang Wu, Chao Zhang, Zhaoqing Li, Tingting Zhu, Jinliang Chen, Yu Ren, Xudong Wang, Lun Zhang, Xuan Zhou Tags: Original Articles Source Type: research
USP9X inhibition improves gemcitabine sensitivity in pancreatic cancer by inhibiting autophagy
Gemcitabine is the cornerstone of pancreatic cancer treatment. Although effective in most patients, development of tumor resistance to gemcitabine can critically limit its efficacy. The mechanisms responsible for this phenomenon remain elusive, but evidence suggests that ubiquitin-specific peptidases (USPs) may be key regulators in cancer chemo-resistance. The present study aimed to investigate the role of USP9X in gemcitabine resistance using in vitro pancreatic cell lines and a mouse xenograft model. (Source: Cancer Letters)
Source: Cancer Letters - August 14, 2018 Category: Cancer & Oncology Authors: Tao Ma, Wei Chen, Xiao Zhi, Hao Liu, Yue Zhou, Brayant Wei Chen, Liqiang Hu, Jian Shen, Xiaoxiao Zheng, Shufen Zhang, Tingbo Liang Tags: Original Articles Source Type: research
PTEN deficiency confers colorectal cancer cell resistance to dual inhibitors of FLT3 and aurora kinase A
PTEN is a tumor suppressor found mutated in many cancers. From a synthetic lethality drug screen with PTEN-isogenic colorectal cancer cells, we found that mutant-PTEN cells were resistant to dual inhibitors of FLT3 and aurora kinase-A, including KW2449 and ENMD-2076. KW2449 significantly reduced the viability of wildtype-PTEN cells causing apoptosis, while little effect was observed in mutant-PTEN counterparts. Transcriptome profiling showed that members of PI3K-AKT signaling pathway were strongly changed in cells after KW2449 treatment, indicating a potential role of the pathway in drug resistance. (Source: Cancer Letters)
Source: Cancer Letters - August 14, 2018 Category: Cancer & Oncology Authors: Yifan Liu, Eun Ju Yang, Baoyuan Zhang, Zhengqiang Miao, Changjie Wu, Junfang Lyu, Kaeling Tan, Terence Chuen Wai Poon, Joong Sup Shim Tags: Original Articles Source Type: research
Tim-4 promotes the growth of colorectal cancer by activating angiogenesis and recruiting tumor-associated macrophages via the PI3K/AKT/mTOR signaling pathway
In this study, we investigated the physiological alterations and molecular events related to Tim-4 overexpression in a mouse model of colorectal cancer (CRC). In the current study, we observed that Tim-4 is upregulated in CRC tissues compared with neighboring normal tissues. In addition, statistical analysis revealed that elevated Tim-4 expression was strongly linked to distant metastasis, TNM stage and reduced overall survival duration in CRC patients. (Source: Cancer Letters)
Source: Cancer Letters - August 14, 2018 Category: Cancer & Oncology Authors: Xiao Tan, Zhongqiang Zhang, Hongliang Yao, Liangfang Shen Tags: Original Articles Source Type: research
Exosomal Transfer of miR-151a Enhances Chemosensitivity to Temozolomide in Drug-resistant Glioblastoma
Chemoresistance blunts the effect of Temozolomide (TMZ) in the treatment of glioblastoma multiforme (GBM). Whether exosomal transfer of miRNAs derived from TMZ-resistant GBM cells could confer TMZ resistance remains to be determined. qPCR was used to determine miR-151a expression in two TMZ-resistant GBM cell lines. The direct targets of miR-151a were identi fied by microarray assays, bioinformatics and further RNA chromatin immunoprecipitation (RNA-ChIP) assay. We characterized exosomes from TMZ-resistant cell lines, serum and cerebrospinal fluid (CSF) and determined the effect of exosomes from TMZ-resistant cells on rec...
Source: Cancer Letters - August 10, 2018 Category: Cancer & Oncology Authors: Ailiang Zeng, Zhiyun Wei, Wei Yan, Jianxing Yin, Xiaoxu Huang, Xu Zhou, Rui Li, Feng Shen, Weining Wu, Xiefeng Wang, Yongping You Tags: Original Articles Source Type: research
Fatty Acid Oxidation: An Emerging Facet of Metabolic Transformation in Cancer
Cancer cells undergo metabolic reprogramming such as enhanced aerobic glycolysis, mutations in the tricarboxylic acid cycle enzymes, and upregulation of de novo lipid synthesis and glutaminolysis. These alterations are pivotal to the development and maintenance of the malignant phenotype of cancer cells in unfavorable tumor microenvironment or metastatic sites. Although mitochondrial fatty acid β-oxidation (FAO) is a primary bioenergetic source, it has not been generally recognized as part of the metabolic landscape of cancer. (Source: Cancer Letters)
Source: Cancer Letters - August 10, 2018 Category: Cancer & Oncology Authors: Yibao Ma, Sarah M. Temkin, Adam M. Hawkridge, Chunqing Guo, Wei Wang, Xiang-Yang Wang, Xianjun Fang Tags: Mini-review Source Type: research
Exosomes derived from hypoxic epithelial ovarian cancer cells deliver microRNAs to macrophages and elicit a tumor-promoted phenotype
In this study, we revealed that exosomes derived from EOC cells remodel macrophages to a tumor-promoted phenotype, namely TAMs. In addition, hypoxic microenvironments have been postulated to facilitate this process in the TME, and hypoxia-inducible factors (HIFs) play an important role in this process. (Source: Cancer Letters)
Source: Cancer Letters - August 8, 2018 Category: Cancer & Oncology Authors: Xin Chen, Jieru Zhou, Xiaoduan Li, Xinjing Wang, Yingying Lin, Xipeng Wang Tags: Original Articles Source Type: research
cAMP/PKA-induced filamin A (FLNA) phosphorylation inhibits SST2 signal transduction in GH-secreting pituitary tumor cells
An efficient intracellular response to somatostatin analogs (SSA) in pituitary tumors requires filamin A (FLNA). Since cAMP pathway plays an important role in GH-secreting pituitary tumors pathogenesis and FLNA is phosphorylated by PKA on S2152, aim of this study was to investigate in tumoral somatotrophs the impact of cAMP pathway activation and SSA stimulation on FLNA phosphorylation and the consequences on SST2 function.We found a PKA-mediated increase (2-fold) and SST2 agonist-induced decrease (-50%) of FLNA phosphorylation in GH3, GH4C1 and primary somatotroph tumor cells. (Source: Cancer Letters)
Source: Cancer Letters - August 8, 2018 Category: Cancer & Oncology Authors: E. Peverelli, E. Giardino, F. Mangili, D. Treppiedi, R. Catalano, E. Ferrante, E. Sala, M. Locatelli, A.G. Lania, M. Arosio, A. Spada, G. Mantovani Tags: Original Articles Source Type: research
Tannins from Syzygium guineense suppress Wnt signaling and proliferation of Wnt-dependent tumors through a direct effect on secreted Wnts
We examined extracts from several indigenous Cameroonian herbs and tested their effects on proliferation and Wnt signaling in TNBC and CC cells. (Source: Cancer Letters)
Source: Cancer Letters - August 8, 2018 Category: Cancer & Oncology Authors: Alexey Koval, Constant A. Pieme, Emerson Ferreira Queiroz, Simone Ragusa, Kamal Ahmed, Artem Blagodatski, Jean-Luc Wolfender, Tatiana V. Petrova, Vladimir L. Katanaev Tags: Original Articles Source Type: research
β-catenin contributes to cordycepin-induced MGMT inhibition and reduction of temozolomide resistance in glioma cells by increasing intracellular reactive oxygen species
Glioblastoma multiforme (GBM) is one of the most aggressive human tumors, and it has a poor prognosis. Temozolomide (TMZ) is the primary alkylating agent used to treat GBM. Nevertheless, a number of GBM patients are resistant to TMZ. Therefore, there is an urgent need for more effective therapeutic options. Cordycepin (COR) is a natural chemical with anti-tumor effects, although its mechanism of action is poorly understood. Several lines of evidence suggest that O6-methylguanine DNA methyltransferase (MGMT) repairs damaged DNA and contributes to drug resistance to TMZ in gliomas. (Source: Cancer Letters)
Source: Cancer Letters - August 3, 2018 Category: Cancer & Oncology Authors: Yiming Bi, Han Li, Dazhuang Yi, Yang Bai, Sheng Zhong, Qiaochu Liu, Yong Chen, Gang Zhao Tags: Original Articles Source Type: research
S100B Suppression Alters Polarization of Infiltrating Myeloid-Derived Cells in Gliomas and Inhibits Tumor Growth
S100B, a member of the multigene family of Ca2+-binding proteins, is overexpressed by most malignant gliomas but its biological role in gliomagenesis is unclear. Recently, we demonstrated that low concentrations of S100B attenuated microglia activation through the induction of STAT3. Furthermore, S100B downregulation in a murine glioma model inhibited macrophage trafficking and tumor growth. Based on these observations, we hypothesized that S100B inhibitors may have antiglioma properties through modulation of tumor microenvironment. (Source: Cancer Letters)
Source: Cancer Letters - August 2, 2018 Category: Cancer & Oncology Authors: Hang Gao, Ian Y. Zhang, Leying Zhang, Yanyan Song, Shunan Liu, Hui Ren, Huili Liu, Hui Zhou, Yanping Su, Yihang Yang, Behnam Badie Tags: Original Articles Source Type: research
Novel CIL-102 Derivatives as Potential Therapeutic Agents for Docetaxel-Resistant Prostate Cancer
In this study, we modified the structure of CIL-102 and investigated the efficacy of the derivatives against CRPC and docetaxel-resistant PCa. (Source: Cancer Letters)
Source: Cancer Letters - August 2, 2018 Category: Cancer & Oncology Authors: Dannah R. Miller, Cherng-Chyi Tzeng, Trey Farmer, Evan T. Keller, Steve Caplan, Yu-Shuin Chen, Yeh-Long Chen, Ming-Fong Lin Tags: Original Articles Source Type: research
Hypertonicity-imposed BCL-XL addiction primes colorectal cancer cells for death
Induction of mitochondria-controlled (intrinsic) apoptosis is a mainstay of current anti-neoplastic chemotherapies. Activation of this death pathway is counteracted by BCL-2-like proteins, which functionally set the threshold for apoptosis and determine whether malignant cells are sensitive or resistant to anti-cancer treatments. Hence, unlocking the intrinsic apoptotic cascade and promoting the cell's commitment to undergo apoptosis concordantly promotes efficacy of anti-cancer treatments. Here, we show that hyperosmotic stress enforces addiction of colorectal cancer cells to BCL-XL, thereby exhausting the protective capa...
Source: Cancer Letters - August 1, 2018 Category: Cancer & Oncology Authors: Sina Heimer, Gertrud Knoll, Charlotte Steixner, Diana Nicoleta Calance, Dieu Thuy Trinh, Martin Ehrenschwender Tags: Original Articles Source Type: research
