265 results found
Lam E, Activation of Aurora A Kinase Increases YAP Stability via Blockage of Autophagy, Cell Death and Disease, ISSN: 2041-4889
Mahmud Z, Asaduzzaman M, Kumar U, et al., 2019, Oncogenic EP300 can be targeted with inhibitors of aldo-keto reductases, BIOCHEMICAL PHARMACOLOGY, Vol: 163, Pages: 391-403, ISSN: 0006-2952
Monteiro LJ, Cubillos S, Sanchez M, et al., 2019, Reduced FOXM1 Expression Limits Trophoblast Migration and Angiogenesis and Is Associated With Preeclampsia., Reprod Sci, Vol: 26, Pages: 580-590
Trophoblast cells are often compared to highly invasive carcinoma cells due to their capacity to proliferate in hypoxic conditions and to exhibit analogous vascular, proliferative, migratory, and invasive capacities. Thus, genes that are important for tumorigenesis, such as forkhead box M1 ( FOXM1) may also be involved in processes of trophoblast invasion. Indeed, we found Foxm1 protein and messenger RNA (mRNA) levels decreased as gestational age increased in rat's placentae. Accordingly, when mimicking early placental events in vitro, protein and mRNA expression of FOXM1 increased from 21% to 8% O2, reaching its highest expression at 3% oxygen tension, which reflects early implantation environment, and dropping to very low levels at 1% O2. Remarkably, FOXM1 silencing in JEG-3 cells was able to significantly decrease migration by 27.9%, in comparison with those cells transfected with control siRNA. Moreover, angiogenesis was compromised when conditioned media (CM) from FOXM1-siRNA -JEG-3 (3% O2) was added to human umbilical vein endothelial cells (HUVEC) cells; however, when CM of JEG-3 cells overexpressing FOXM1 at 1% O2 was added, the ability of HUVEC to form tubule networks was restored. Additionally, quantitative real-time polymerase chain reaction (PCR) assays of FOXM1 knockdown and overexpression experiments in JEG-3 cells revealed that the depletion of FOXM1 at 3% O2 and overexpression of FOXM1 at 1% O2 led to downregulation and upregulation of vascular endothelial growth factor transcriptional (VEGF) levels, respectively. Conversely, we also observed deregulation of FOXM1 in placentae derived from pregnancies complicated by preeclampsia (PE). Therefore, we demonstrate that FOXM1 may be a new regulatory protein of early placentation processes and that under chronic hypoxic conditions (1% O2) and in patients with severe PE, its levels decrease.
Liu N, Cui W, Jiang X, et al., 2019, The critical role of dysregulated RhoB signaling pathway in radioresistance of colorectal cancer., Int J Radiat Oncol Biol Phys
PURPOSE: To explore whether Rho protein was involved in the radioresistance of colorectal cancer and investigated the underlying mechanism. METHODS AND MATERIALS: Rho GTPase expression was measured after radiation treatment in colon cancer cells. RhoB knockout cell lines were established by CRISPR/Cas9 system. In vitro assays and zebrafish embryos were used for analyzing radiosensitivity and invasive ability. Mass cytometry was for detecting RhoB downstream signaling factors. RhoB and FOXM1 expression were detected by immunohistochemistry in rectal cancer patients who participated in a radiotherapy trial. RESULTS: RhoB expression was related to radiation resistance. Complete depletion of RhoB protein increased radiosensitivity and impaired radiation-enhanced metastatic potential in vitro and in zebrafish model. Probing signaling using mass cytometry-based single-cell analysis showed that Akt phosphorylation level was inhibited by RhoB depletion after radiation. FOXM1 was downregulated in RhoB knockout cells and the inhibition of FOXM1 led to lower survival rates, and attenuated migration and invasion abilities of the cells after radiation. In the patients with radiotherapy, RhoB overexpression was related to high FOXM1, late TNM stage, high distant recurrence and poor survival independent of other clinical factors. CONCLUSIONS: RhoB plays a critical role in radioresistance of colorectal cancer through Akt and FOXM1 pathway.
Parzych K, Saavedra-Garcia P, Valbuena GN, et al., 2019, The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation, ONCOGENE, Vol: 38, Pages: 3216-3231, ISSN: 0950-9232
Sachini N, Arampatzi P, Klonizakis A, et al., 2019, Promyelocytic leukemia protein (PML) controls breast cancer cell proliferation by modulating Forkhead transcription factors., Mol Oncol
The multitasking promyelocytic leukemia (PML) protein was originally recognized as a tumor-suppressive factor, but more recent evidence has implicated PML in tumor cell prosurvival actions and poor patient prognosis in specific cancer settings. Here, we report that inducible PMLIV expression inhibits cell proliferation as well as self-renewal and impairs cell cycle progression of breast cancer cell lines in a reversible manner. Transcriptomic profiling identified a large number of PML-deregulated genes associated with various cell processes. Among them, cell cycle- and division-related genes and their cognitive regulators are highly ranked. In this study, we focused on previously unknown PML targets, namely the Forkhead transcription factors. PML suppresses the Forkhead box subclass M1 (FOXM1) transcription factor at both the RNA and protein levels, along with many of its gene targets. We show that FOXM1 interacts with PMLIV primarily via its DNA-binding domain and dynamically colocalizes in PML nuclear bodies. In parallel, PML modulates the activity of Forkhead box O3 (FOXO3), a factor opposing certain FOXM1 activities, to promote cell survival and stress resistance. Thus, PMLIV affects the balance of FOXO3 and FOXM1 transcriptional programs by acting on discrete gene subsets to favor both growth inhibition and survival. Interestingly, PMLIV-specific knockdown mimicked ectopic expression vis-à-vis loss of proliferative ability and self-renewal, but also led to loss of survival ability as shown by increased apoptosis. We propose that divergent or similar effects on cell physiology may be elicited by high or low PMLIV levels dictated by other concurrent genetic or epigenetic cancer cell states that may additionally account for its disparate effects in various cancer types.
Han L, Lam EW-F, Sun Y, 2019, Extracellular vesicles in the tumor microenvironment: old stories, but new tales., Mol Cancer, Vol: 18
Mammalian cells synthesize and release heterogeneous extracellular vesicles (EVs) which can be generally recognized as subclasses including exosomes, microvesicles (MVs), and apoptotic bodies (ABs), each differing in their biogenesis, composition and biological functions from others. EVs can originate from normal or cancer cells, transfer bioactive cargoes to both adjacent and distant sites, and orchestrate multiple key pathophysiological events such as carcinogenesis and malignant progression. Emerging as key messengers that mediate intercellular communications, EVs are being paid substantial attention in various disciplines including but not limited to cancer biology and immunology. Increasing lines of research advances have revealed the critical role of EVs in the establishment and maintenance of the tumor microenvironment (TME), including sustaining cell proliferation, evading growth suppression, resisting cell death, acquiring genomic instability and reprogramming stromal cell lineages, together contributing to the generation of a functionally remodeled TME. In this article, we present updates on major topics that document how EVs are implicated in proliferative expansion of cancer cells, promotion of drug resistance, reprogramming of metabolic activity, enhancement of metastatic potential, induction of angiogenesis, and escape from immune surveillance. Appropriate and insightful understanding of EVs and their contribution to cancer progression can lead to new avenues in the prevention, diagnosis and treatment of human malignancies in future medicine.
Nestal de Moraes G, Carneiro LDT, Maia RC, et al., 2019, FOXK2 Transcription Factor and Its Emerging Roles in Cancer., Cancers (Basel), Vol: 11, ISSN: 2072-6694
Forkhead box (FOX) transcription factors compose a large family of regulators of key biological processes within a cell. FOXK2 is a member of FOX family, whose biological functions remain relatively unexplored, despite its description in the early nineties. More recently, growing evidence has been pointing towards a role of FOXK2 in cancer, which is likely to be context-dependent and tumour-specific. Here, we provide an overview of important aspects concerning the mechanisms of regulation of FOXK2 expression and function, as well as its complex interactions at the chromatin level, which orchestrate how it differentially regulates the expression of gene targets in pathophysiology. Particularly, we explore the emerging functions of FOXK2 as a regulator of a broad range of cancer features, such as cell proliferation and survival, DNA damage, metabolism, migration, invasion and metastasis. Finally, we discuss the prognostic value of assessing FOXK2 expression in cancer patients and how it can be potentially targeted for future anticancer interventions.
Karadedou CT, Gomes AR, Chen J, et al., 2019, Correction: FOXO3a represses VEGF expression through FOXM1-dependent and -independent mechanisms in breast cancer., Oncogene
In the published version of this article, the images for cytoplasmic and nuclear FGF7 in MDA-MB-231 cells were duplicated and mistaken for total FGF7 in SKBR-3 and MDA-MB-231 cells.
Cui B, Luo Y, Tian P, et al., 2019, Stress-induced epinephrine enhances lactate dehydrogenase A and promotes breast cancer stem-like cells, JOURNAL OF CLINICAL INVESTIGATION, Vol: 129, Pages: 1030-1046, ISSN: 0021-9738
He B, Gao R, Lv D, et al., 2019, The prognostic landscape of interactive biological processes presents treatment responses in cancer, EBIOMEDICINE, Vol: 41, Pages: 120-133, ISSN: 2352-3964
Varghese V, Magnani L, Harada-Shoji N, et al., 2019, FOXM1 modulates 5-FU resistance in colorectal cancer through regulating TYMS expression, SCIENTIFIC REPORTS, Vol: 9, ISSN: 2045-2322
Zhang B, Lam EW-F, Sun Y, 2019, Senescent cells: A new Achilles' heel to exploit for cancer medicine?, Aging Cell, Vol: 18
Cellular senescence is a typical tumor-suppressive mechanism that restricts the proliferation of premalignant cells. However, mounting evidence suggests that senescent cells, which also persist in vivo, can promote the incidence of aging-related disorders principally via the senescence-associated secretory phenotype (SASP), among which cancer is particularly devastating. Despite the beneficial effects of the SASP on certain physiological events such as wound healing and tissue repair, more studies have demonstrated that senescent cells can substantially contribute to pathological conditions and accelerate disease exacerbation, particularly cancer resistance, relapse and metastasis. To limit the detrimental properties while retaining the beneficial aspects of senescent cells, research advancements that support screening, design and optimization of anti-aging therapeutic agents are in rapid progress in the setting of prospective development of clinical strategies, which together represent a new wave of efforts to control human malignancies or mitigate degenerative complications.
FOXO3 is a tumor suppressor that orchestrates the expression of genes that regulate cell cycle progression, apoptosis, metabolism, oxidative stress, and other important cellular processes. Its inactivation is closely associated with tumorigenesis and cancer progression. On the other hand, sirtuin proteins have been demonstrated to be able to deacetylate, thus causing FOXO3 inactivation at the posttranslational level. Therefore, targeting sirtuin proteins renders new avenues for breast cancer treatment. Here, we describe three procedures for studying FOXO3 posttranslational modifications controlled by sirtuin proteins in cancer cells.
Intuyod K, Saavedra-Garcia P, Zona S, et al., 2018, FOXM1 modulates 5-fluorouracil sensitivity in cholangiocarcinoma through thymidylate synthase (TYMS): implications of FOXM1-TYMS axis uncoupling in 5-FU resistance, CELL DEATH & DISEASE, Vol: 9, ISSN: 2041-4889
Vervoort SJ, de Jong OG, Roukens MG, et al., 2018, Gloal transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis, ELIFE, Vol: 7, ISSN: 2050-084X
Li M, Chai H-F, Peng F, et al., 2018, Estrogen receptor beta upregulated by lncRNA-H19 to promote cancer stem-like properties in papillary thyroid carcinoma, CELL DEATH & DISEASE, Vol: 9, ISSN: 2041-4889
Wahba J, Natoli M, Whilding LM, et al., 2018, Chemotherapy-induced apoptosis, autophagy and cell cycle arrest are key drivers of synergy in chemo-immunotherapy of epithelial ovarian cancer, CANCER IMMUNOLOGY IMMUNOTHERAPY, Vol: 67, Pages: 1753-1765, ISSN: 0340-7004
Phoomak C, Silsirivanit A, Park D, et al., 2018, O-GlcNAcylation mediates metastasis of cholangiocarcinoma through FOXO3 and MAN1A1, ONCOGENE, Vol: 37, Pages: 5648-5665, ISSN: 0950-9232
Chen F, Long Q, Fu D, et al., 2018, Targeting SPINK1 in the damaged tumour microenvironment alleviates therapeutic resistance, NATURE COMMUNICATIONS, Vol: 9, ISSN: 2041-1723
Sun Y, Coppe J-P, Lam EW-F, 2018, Cellular Senescence: The Sought or the Unwanted?, TRENDS IN MOLECULAR MEDICINE, Vol: 24, Pages: 871-885, ISSN: 1471-4914
Gong C, Man EPS, Tsoi H, et al., 2018, BQ323636.1, a Novel Splice Variant to NCOR2, as a Predictor for Tamoxifen-Resistant Breast Cancer, CLINICAL CANCER RESEARCH, Vol: 24, Pages: 3681-3691, ISSN: 1078-0432
Yao S, Fan LY-N, Lam EW-F, 2018, The FOXO3-FOXM1 axis: A key cancer drug target and a modulator of cancer drug resistance, SEMINARS IN CANCER BIOLOGY, Vol: 50, Pages: 77-89, ISSN: 1044-579X
Laphanuwat P, Likasitwatanakul P, Sittithumcharee G, et al., 2018, Cyclin D1 depletion interferes with oxidative balance and promotes cancer cell senescence, JOURNAL OF CELL SCIENCE, Vol: 131, ISSN: 0021-9533
Laphanuwat P, Likasitwatanakul P, Sittithumcharee G, et al., 2018, Cyclin D1 depletion interferes with oxidative balance and promotes cancer cell senescence, Journal of Cell Science, Vol: 131, ISSN: 0021-9533
© 2018. Published by The Company of Biologists Ltd. Expression of cyclin D1 (CCND1) is required for cancer cell survival and proliferation. This is presumably due to the role of cyclin D1 in inactivation of the RB tumor suppressor. Here, we investigated the pro-survival function of cyclin D1 in a number of cancer cell lines. We found that cyclin D1 depletion facilitated cellular senescence in several cancer cell lines. Senescence triggered by cyclin D1 depletion was more extensive than that caused by the prolonged CDK4 inhibition. Intriguingly, the senescence caused by cyclin D1 depletion was independent of RB status of the cancer cell. We identified a build-up of intracellular reactive oxygen species in the cancer cells that underwent senescence upon depletion of cyclin D1 but not in those cells where CDK4 was inhibited. The higher ROS levels were responsible for the cell senescence, which was instigated by the p38-JNKFOXO3a- p27 pathway. Therefore, expression of cyclin D1 prevents cancer cells from undergoing senescence, at least partially, by keeping the level of intracellular oxidative stress at a tolerable sublethal level. Depletion of cyclin D1 promotes the RB-independent pro-senescence pathway and the cancer cells then succumb to the endogenous oxidative stress levels.
Zhang B, Fu D, Xu Q, et al., 2018, The senescence-associated secretory phenotype is potentiated by feedforward regulatory mechanisms involving Zscan4 and TAK1, NATURE COMMUNICATIONS, Vol: 9, ISSN: 2041-1723
de Moraes GN, Ji Z, Fan LY-N, et al., 2018, SUMOylation modulates FOXK2-mediated paclitaxel sensitivity in breast cancer cells, ONCOGENESIS, Vol: 7, ISSN: 2157-9024
Peng F, Wang J-H, Fan W-J, et al., 2018, Glycolysis gatekeeper PDK1 reprograms breast cancer stem cells under hypoxia, ONCOGENE, Vol: 37, Pages: 1062-1074, ISSN: 0950-9232
Peng F, Wang J-H, Fan W-J, et al., 2018, Glycolysis gatekeeper PDK1 reprograms breast cancer stem cells under hypoxia (vol 37, pg 1062, 2017), ONCOGENE, Vol: 37, Pages: 1119-1119, ISSN: 0950-9232
Alasiri G, Fan LY-N, Zona S, et al., 2018, ER stress and cancer: The FOXO forkhead transcription factor link, MOLECULAR AND CELLULAR ENDOCRINOLOGY, Vol: 462, Pages: 67-81, ISSN: 0303-7207
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