bims-ectoca Biomed News
on Epigenetic control of tolerance in cancer
Issue of 2023‒05‒21
fourteen papers selected by
Ankita Daiya
BITS Pilani
  1. Deciphering the involvement of the Hippo pathway co-regulators, YAP/TAZ in invadopodia formation and matrix degradation.
  2. The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase.
  3. Deubiquitinating enzyme USP10 promotes osteosarcoma metastasis and epithelial-mesenchymal transition by stabilizing YAP1.
  4. Toward a systems-level probing of tumor clonality.
  5. Mitochondrial Dynamics: Working with the Cytoskeleton and Intracellular Organelles to Mediate Mechanotransduction.
  6. Cisplatin-Resistant Ovarian Cancer Cells Reveal a Polyploid Phenotype with Remarkable Activation of Nuclear Processes.
  7. The metastatic niche formation: focus on extracellular vesicle-mediated dialogue between lung cancer cells and the microenvironment.
  8. Hypoxia-mediated promotion of glucose metabolism in non-small cell lung cancer correlates with activation of the EZH2/FBXL7/PFKFB4 axis.
  9. Association of nanoparticles and Nrf2 with various oxidative stress-mediated diseases.
  10. BRAFV600E restructures cellular lactylation to promote anaplastic thyroid cancer proliferation.
  11. First-Line Combination Treatment with Low-Dose Bipolar Drugs for ABCB1-Overexpressing Drug-Resistant Cancer Populations.
  12. Nuclear morphology predicts cell survival to cisplatin chemotherapy.
  13. Osteocytes: New Kids on the Block for Cancer in Bone Therapy.
  14. Integrated In Silico Analysis of Proteogenomic and Drug Targets for Pancreatic Cancer Survival.
  1. Cell Death Dis. 2023 Apr 25. 14(4): 290
    Deciphering the involvement of the Hippo pathway co-regulators, YAP/TAZ in invadopodia formation and matrix degradation.
    Jubina Balan Venghateri, Bareket Dassa, David Morgenstern, Michal Shreberk-Shaked, Moshe Oren, Benjamin Geiger.
      Invadopodia are adhesive, actin-rich protrusions formed by metastatic cancer cells that degrade the extracellular matrix and facilitate invasion. They support the metastatic cascade by a spatially and temporally coordinated process whereby invading cells bind to the matrix, degrade it by specific metalloproteinases, and mechanically penetrate diverse tissue barriers by forming actin-rich extensions. However, despite the apparent involvement of invadopodia in the metastatic process, the molecular mechanisms that regulate invadopodia formation and function are still largely unclear. In this study, we have explored the involvement of the key Hippo pathway co-regulators, namely YAP, and TAZ, in invadopodia formation and matrix degradation. Toward that goal, we tested the effect of depletion of YAP, TAZ, or both on invadopodia formation and activity in multiple human cancer cell lines. We report that the knockdown of YAP and TAZ or their inhibition by verteporfin induces a significant elevation in matrix degradation and invadopodia formation in several cancer cell lines. Conversely, overexpression of these proteins strongly suppresses invadopodia formation and matrix degradation. Proteomic and transcriptomic profiling of MDA-MB-231 cells, following co-knockdown of YAP and TAZ, revealed a significant change in the levels of key invadopodia-associated proteins, including the crucial proteins Tks5 and MT1-MMP (MMP14). Collectively, our findings show that YAP and TAZ act as negative regulators of invadopodia formation in diverse cancer lines, most likely by reducing the levels of essential invadopodia components. Dissecting the molecular mechanisms of invadopodia formation in cancer invasion may eventually reveal novel targets for therapeutic applications against invasive cancer.
    DOI:  https://doi.org/10.1038/s41419-023-05769-1
  2. Epigenetics Chromatin. 2023 May 13. 16(1): 18
    The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase.
    Eva Monte-Serrano, Patricia Morejón-García, Ignacio Campillo-Marcos, Aurora Campos-Díaz, Elena Navarro-Carrasco, Pedro A Lazo.
      BACKGROUND: Dynamic chromatin remodeling is associated with changes in the epigenetic pattern of histone acetylations and methylations required for processes based on dynamic chromatin remodeling and implicated in different nuclear functions. These histone epigenetic modifications need to be coordinated, a role that may be mediated by chromatin kinases such as VRK1, which phosphorylates histones H3 and H2A.METHODS: The effect of VRK1 depletion and VRK1 inhibitor, VRK-IN-1, on the acetylation and methylation of histone H3 in K4, K9 and K27 was determined under different conditions, arrested or proliferating cells, in A549 lung adenocarcinoma and U2OS osteosarcoma cells.
    RESULTS: Chromatin organization is determined by the phosphorylation pattern of histones mediated by different types of enzymes. We have studied how the VRK1 chromatin kinase can alter the epigenetic posttranslational modifications of histones by using siRNA, a specific inhibitor of this kinase (VRK-IN-1), and of histone acetyl and methyl transferases, as well as histone deacetylase and demethylase. Loss of VRK1 implicated a switch in the state of H3K9 posttranslational modifications. VRK1 depletion/inhibition causes a loss of H3K9 acetylation and facilitates its methylation. This effect is similar to that of the KAT inhibitor C646, and to KDM inhibitors as iadademstat (ORY-1001) or JMJD2 inhibitor. Alternatively, HDAC inhibitors (selisistat, panobinostat, vorinostat) and KMT inhibitors (tazemetostat, chaetocin) have the opposite effect of VRK1 depletion or inhibition, and cause increase of H3K9ac and a decrease of H3K9me3. VRK1 stably interacts with members of these four enzyme families. However, VRK1 can only play a role on these epigenetic modifications by indirect mechanisms in which these epigenetic enzymes are likely targets to be regulated and coordinated by VRK1.
    CONCLUSIONS: The chromatin kinase VRK1 regulates the epigenetic patterns of histone H3 acetylation and methylation in lysines 4, 9 and 27. VRK1 is a master regulator of chromatin organization associated with its specific functions, such as transcription or DNA repair.
    Keywords:  Acetylation; Chromatin; Histone H3; Kinase; Methylation; VRK-IN-1
    DOI:  https://doi.org/10.1186/s13072-023-00494-7
  3. Cancer Med. 2023 May 15.
    Deubiquitinating enzyme USP10 promotes osteosarcoma metastasis and epithelial-mesenchymal transition by stabilizing YAP1.
    Jianyong Deng, Xuan Yi, Zuxi Feng, Jie Peng, Dan Li, Chen Li, Binbin Deng, Shuaigang Liu, Souradeep Sahu, Liang Hao.
      BACKGROUND: Osteosarcoma (OS) is a fatal adolescent tumor, which is susceptible to remote metastases at an early stage, and its treatment remains a major challenge. ubiquitin-specific protease 10 (USP10) is primarily located in the cytoplasm and can therefore deubiquitinate various cytoplasmic proteins. However, the expression and mechanism of USP10 in OS remain ambiguous. The aim of this study was to explore how USP10 affects Yes-associated protein1 (YAP1) to influence the metastasis and epithelial-mesenchymal transition (EMT).METHODS: Western blotting, qRT-PCR, and immunohistochemical (IHC) analyses were performed to evaluate USP10 and YAP1 levels. Using wound healing and transwell tests, the roles and molecular pathways of USP10 and YAP1 ability to migrate and invade of OS were investigated, and cell morphological alterations were examined using phalloidin staining.
    RESULTS: Our results indicated that USP10, a new type of deubiquitinating protease, is increased in OS tissues and cells contrasted with adjacent healthy tissues. Overexpression of USP10 correlated with tumor size, distant metastasis, and TNM stage, and was an independent factor of poor prognosis in OS patients. Also, USP10 expression is closely connected with the incident of OS metastasis and tumor size. Functional assays revealed that USP10 knockdown suppressed cell migrating and invading ability and inhibited the EMT of OS cells in vivo and in vitro. In addition, we showed that USP10 knockdown decreased the levels of YAP1, which is an important positive regulator of migration and invasion in many cancers. We also found a significant positive correlation between USP10 and YAP1 levels, further demonstrating that USP10-induced migration and EMT are based on YAP1 in OS cells. In a mechanistic way, USP10 stabilizes the expression of YAP1 by mediating its deubiquitination in OS cells.
    CONCLUSION: Together, this study showed that USP10 can directly interact with YAP1 to reduce ubiquitinated YAP1, thereby stabilizing its protein levels and affecting EMT and distant metastasis in OS cells.
    Keywords:  EMT; USP10; YAP1; deubiquitination; osteosarcoma
    DOI:  https://doi.org/10.1002/cam4.6074
  4. iScience. 2023 May 19. 26(5): 106574
    Toward a systems-level probing of tumor clonality.
    Emanuelle I Grody, Ajay Abraham, Vipul Shukla, Yogesh Goyal.
      Cancer has been described as a genetic disease that clonally evolves in the face of selective pressures imposed by cell-intrinsic and extrinsic factors. Although classical models based on genetic data predominantly propose Darwinian mechanisms of cancer evolution, recent single-cell profiling of cancers has described unprecedented heterogeneity in tumors providing support for alternative models of branched and neutral evolution through both genetic and non-genetic mechanisms. Emerging evidence points to a complex interplay between genetic, non-genetic, and extrinsic environmental factors in shaping the evolution of tumors. In this perspective, we briefly discuss the role of cell-intrinsic and extrinsic factors that shape clonal behaviors during tumor progression, metastasis, and drug resistance. Taking examples of pre-malignant states associated with hematological malignancies and esophageal cancer, we discuss recent paradigms of tumor evolution and prospective approaches to further enhance our understanding of this spatiotemporally regulated process.
    Keywords:  Cancer; Cancer systems biology; Immunology
    DOI:  https://doi.org/10.1016/j.isci.2023.106574
  5. Aging Dis. 2023 Feb 15.
    Mitochondrial Dynamics: Working with the Cytoskeleton and Intracellular Organelles to Mediate Mechanotransduction.
    Danyuan Huang, Shuo Chen, Ding Xiong, Han Wang, Li Zhu, Yuanyuan Wei, Yuyu Li, Shujuan Zou.
      Cells are constantly exposed to various mechanical environments; therefore, it is important that they are able to sense and adapt to changes. It is known that the cytoskeleton plays a critical role in mediating and generating extra- and intracellular forces and that mitochondrial dynamics are crucial for maintaining energy homeostasis. Nevertheless, the mechanisms by which cells integrate mechanosensing, mechanotransduction, and metabolic reprogramming remain poorly understood. In this review, we first discuss the interaction between mitochondrial dynamics and cytoskeletal components, followed by the annotation of membranous organelles intimately related to mitochondrial dynamic events. Finally, we discuss the evidence supporting the participation of mitochondria in mechanotransduction and corresponding alterations in cellular energy conditions. Notable advances in bioenergetics and biomechanics suggest that the mechanotransduction system composed of mitochondria, the cytoskeletal system, and membranous organelles is regulated through mitochondrial dynamics, which may be a promising target for further investigation and precision therapies.
    DOI:  https://doi.org/10.14336/AD.2023.0201
  6. Adv Biomed Res. 2023 ;12 77
    Cisplatin-Resistant Ovarian Cancer Cells Reveal a Polyploid Phenotype with Remarkable Activation of Nuclear Processes.
    Rezvan Adibi, Shiva Moein, Yousof Gheisari.
      Background: Tumor recurrence as one of the main causes of cancer death is a big barrier to cancer complete treatment. Various studies denote the possible role of therapeutics in tumor relapse. Cisplatin as one of the generally used chemotherapy agents is supposed to be the source of therapy resistance through formation of polyploid giant cancer cells (PGCCs). Nevertheless, the mechanisms by which PGCCs promote tumor relapse are not fully understood.Materials and Methods: In this study, we performed experimental and bioinformatic investigations to recognize the mechanisms related to cisplatin resistance. A2780 and SCOV-3 cell lines were treated with cisplatin for 72 hours and were evaluated for their morphology by fluorescent microscopy and DNA content analysis. Furthermore, a microarray dataset of cisplatin-resistant ovarian cancer cells was re-analyzed to determine the significantly altered genes and signaling pathways.
    Results: Although cisplatin led to death of considerable fraction of cells in both cell lines, a significant number of survived cells became polyploid. On the other hand, our high throughput analysis determined significant change in expression of 1930 genes which mainly related to gene regulatory mechanisms and nuclear processes. Besides, mTOR, hypoxia, Hippo, and 14-3-3 signaling pathways previously shown to have role in PGCCs were determined.
    Conclusion: Taken together, results of this study demonstrated some key biological mechanisms related to cisplatin-resistant polyploid cancer cells.
    Keywords:  Cancer resistance; gene expression profiling; ovary cancer; polyploid cells; systems biology
    DOI:  https://doi.org/10.4103/abr.abr_348_21
  7. Front Oncol. 2023 ;13 1116783
    The metastatic niche formation: focus on extracellular vesicle-mediated dialogue between lung cancer cells and the microenvironment.
    Francesca Pontis, Luca Roz, Orazio Fortunato, Giulia Bertolini.
      Lung cancer is the deadliest cancer in the world, with the majority of patients presenting with advanced or metastatic disease at first diagnosis. The lungs are also one of the most common sites of metastasis from lung cancer and other tumors. Understanding the mechanisms that regulate metastasis formation from primary lung cancer and in the lungs is therefore fundamental unmet clinical need. One of the first steps during the establishment of lung cancer metastases includes the formation of the pre-metastatic niche (PMN) at distant organs, which may occur even during the early phases of cancer development. The PMN is established through intricate cross-talk between primary tumor-secreted factors and stromal components at distant sites. Mechanisms controlling primary tumor escape and seeding of distant organs rely on specific properties of tumor cells but are also tightly regulated by interactions with stromal cells at the metastatic niche that finally dictate the success of metastasis establishment. Here, we summarize the mechanisms underlying pre-metastatic niche formation starting from how lung primary tumor cells modulate distant sites through the release of several factors, focusing on Extracellular Vesicles (EVs). In this context, we highlight the role of lung cancer-derived EVs in the modulation of tumor immune escape. Then, we illustrate the complexity of Circulating Tumor Cells (CTCs) that represent the seeds of metastasis and how interactions with stromal and immune cells can help their metastatic dissemination. Finally, we evaluate the contribution of EVs in dictating metastasis development at the PMN through stimulation of proliferation and control of disseminated tumor cell dormancy. Overall, we present an overview of different steps in the lung cancer metastatic cascade, focusing on the EV-mediated interactions between tumor cells and stromal/immune cells.
    Keywords:  CTC (circulation tumor cells); dormancy (seed); extracellular vesicles (EV); lung cancer; premetastatic niche
    DOI:  https://doi.org/10.3389/fonc.2023.1116783
  8. Cell Death Dis. 2023 05 13. 14(5): 326
    Hypoxia-mediated promotion of glucose metabolism in non-small cell lung cancer correlates with activation of the EZH2/FBXL7/PFKFB4 axis.
    Jing Zhou, Yang Lin, Xiuhua Kang, Zhicheng Liu, Juntao Zou, Fei Xu.
      F-box/LRR-repeat protein 7 (FBXL7) was predicted as a differentially expressed E3 ubiquitin ligase in non-small cell lung cancer (NSCLC), which has been suggested to influence cancer growth and metastasis. In this study, we aimed to decipher the function of FBXL7 in NSCLC and delineate the upstream and downstream mechanisms. FBXL7 expression was verified in NSCLC cell lines and GEPIA-based tissue samples, after which the upstream transcription factor of FBXL7 was bioinformatically identified. The substrate PFKFB4 of the FBXL7 was screened out by tandem affinity purification coupled with mass-spectrometry (TAP/MS). FBXL7 was downregulated in NSCLC cell lines and tissue samples. FBXL7 ubiquitinated and degraded PFKFB4, thus suppressing glucose metabolism and malignant phenotypes of NSCLC cells. Hypoxia-induced HIF-1α upregulation elevated EZH2 and inhibited FBXL7 transcription and reduced its expression, thus promoting PFKFB4 protein stability. By this mechanism, glucose metabolism and the malignant phenotype were enhanced. In addition, knockdown of EZH2 impeded tumor growth through the FBXL7/PFKFB4 axis. In conclusion, our work reveals that the EZH2/FBXL7/PFKFB4 axis plays a regulatory role in glucose metabolism and tumor growth of NSCLC, which is expected to be potential biomarkers for NSCLC.
    DOI:  https://doi.org/10.1038/s41419-023-05795-z
  9. Chem Biol Interact. 2023 May 13. pii: S0009-2797(23)00202-8. [Epub ahead of print] 110535
    Association of nanoparticles and Nrf2 with various oxidative stress-mediated diseases.
    Rekha Thiruvengadam, Baskar Venkidasamy, Ramkumar Samynathan, Rajakumar Govindasamy, Muthu Thiruvengadam, Jin Hee Kim.
      Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regultes the cellular antioxidant defense system at the posttranscriptional level. During oxidative stress, Nrf2 is released from its negative regulator Kelch-like ECH-associated protein 1 (Keap1) and binds to antioxidant response element (ARE) to transcribe antioxidative metabolizing/detoxifying genes. Various transcription factors like aryl hydrocarbon receptor (AhR) and nuclear factor kappa light chain enhancer of activated B cells (NF-kB) and epigenetic modification including DNA methylation and histone methylation might also regulate the expression of Nrf2. Despite its protective role, Keap1/Nrf2/ARE signaling is considered as a pharmacological target due to its involvement in various pathophysiological conditions such as diabetes, cardiovascular disease, cancer, neurodegenerative diseases, hepatotoxicity and kidney disorders. Recently, nanomaterials have received a lot of attention due to their unique physiochemical properties and are also used in various biological applications, for example, biosensors, drug delivery systems, cancer therapy, etc. In this review, we will be discussing the functions of nanoparticles and Nrf2 as a combined therapy or sensitizing agent and their significance in various diseases such as diabetes, cancer and oxidative stress-mediated diseases.
    Keywords:  Antioxidants; Detoxification; Nanoparticles; Nrf2; Oxidative stress
    DOI:  https://doi.org/10.1016/j.cbi.2023.110535
  10. Endocr Relat Cancer. 2023 May 01. pii: ERC-22-0344. [Epub ahead of print]
    BRAFV600E restructures cellular lactylation to promote anaplastic thyroid cancer proliferation.
    Xumeng Wang, Tianxing Ying, Jimeng Yuan, Yue Wang, Xingyun Su, Shitu Chen, Yurong Zhao, Yuanyuan Zhao, Jinghao Sheng, Lisong Teng, Chi Luo, Weibin Wang.
      Anaplastic thyroid cancer (ATC) is a rare but fatal cancer with BRAF mutation ranging from 30%-50%. Histone lysine lactylation represents a novel epigenetic mark that translates cellular metabolic signals into transcriptional regulation. It is not clear whether the Warburg effect can promote the proliferation of ATC with BRAFV600E mutation via metabolite-mediated histone lactylation. Our study aimed at illustrating how BRAFV600E restructures cellular protein lactylation landscape to boost ATC proliferation, and determining whether blockade of protein lactylation can sensitize mutant ATC to BRAFV600E inhibitors. Western blotting was used to evaluate lactylation status. Aerobic glycolysis was intervened by adding cell-permeable ethyl lactate or using metabolic inhibitors. Chromatin immunoprecipitation and RT-QPCR were applied to analyze the expression of growth-related genes. Different chemical inhibitors were used to inhibit BRAFV600E and other enzymes. ATC cell line derived xenograft model was employed to examine the efficacy of mono and combinatorial therapies. The results showed that aerobic glycolysis in ATC increased global protein lactylation via improving cellular lactate availability. In particular, lactylation on Histone 4 Lysine 12 residue (H4K12La) activated the expression of multiple genes essential for ATC proliferation. Furthermore, oncogenic BRAFV600E boosted glycolytic flux to restructure the cellular lactylation landscape, leading to H4K12La-driven gene transcription and cell cycle deregulation. Accordingly, blockade of cellular lactylation machinery synergized with BRAFV600E inhibitor to impair ATC progression both in vitro and in vivo. Our results demonstrated an extra beneficial effect of aerobic glycolysis on ATC, revealing a novel metabolism-epigenetics axis suitable for combinatorial therapy with BRAFV600E inhibition.
    DOI:  https://doi.org/10.1530/ERC-22-0344
  11. Int J Mol Sci. 2023 May 07. pii: 8389. [Epub ahead of print]24(9):
    First-Line Combination Treatment with Low-Dose Bipolar Drugs for ABCB1-Overexpressing Drug-Resistant Cancer Populations.
    Sungpil Yoon, Hyung Sik Kim.
      Tumors include a heterogeneous population, of which a small proportion includes drug-resistant cancer (stem) cells. In drug-sensitive cancer populations, first-line chemotherapy reduces tumor volume via apoptosis. However, it stimulates drug-resistant cancer populations and finally results in tumor recurrence. Recurrent tumors are unresponsive to chemotherapeutic drugs and are primarily drug-resistant cancers. Therefore, increased apoptosis in drug-resistant cancer cells in heterogeneous populations is important in first-line chemotherapeutic treatments. The overexpression of ABCB1 (or P-gp) on cell membranes is an important characteristic of drug-resistant cancer cells; therefore, first-line combination treatments with P-gp inhibitors could delay tumor recurrence. Low doses of bipolar drugs showed P-gp inhibitory activity, and their use as a combined therapy sensitized drug-resistant cancer cells. FDA-approved bipolar drugs have been used in clinics for a long period of time, and their toxicities are well reported. They can be easily applied as first-line combination treatments for targeting resistant cancer populations. To apply bipolar drugs faster in first-line combination treatments, knowledge of their complete information is crucial. This review discusses the use of low-dose bipolar drugs in sensitizing ABCB1-overexpressing, drug-resistant cancers. We believe that this review will contribute to facilitating first-line combination treatments with low-dose bipolar drugs for targeting drug-resistant cancer populations. In addition, our findings may aid further investigations into targeting drug-resistant cancer populations with low-dose bipolar drugs.
    Keywords:  ABCB1 (or P-gp) overexpression; bipolar drugs; first-line combination treatment; heterogeneous resistant cancer population
    DOI:  https://doi.org/10.3390/ijms24098389
  12. Neoplasia. 2023 May 10. pii: S1476-5586(23)00031-3. [Epub ahead of print]42 100906
    Nuclear morphology predicts cell survival to cisplatin chemotherapy.
    Chi-Ju Kim, Anna Lk Gonye, Kevin Truskowski, Cheng-Fan Lee, Yoon-Kyoung Cho, Robert H Austin, Kenneth J Pienta, Sarah R Amend.
      The emergence of chemotherapy resistance drives cancer lethality in cancer patients, with treatment initially reducing overall tumor burden followed by resistant recurrent disease. While molecular mechanisms underlying resistance phenotypes have been explored, less is known about the cell biological characteristics of cancer cells that survive to eventually seed the recurrence. To identify the unique phenotypic characteristics associated with survival upon chemotherapy exposure, we characterized nuclear morphology and function as prostate cancer cells recovered following cisplatin treatment. Cells that survived in the days and weeks after treatment and resisted therapy-induced cell death showed increasing cell size and nuclear size, enabled by continuous endocycling resulting in repeated whole genome doubling. We further found that cells that survive after therapy release were predominantly mononucleated and likely employ more efficient DNA damage repair. Finally, we show that surviving cancer cells exhibit a distinct nucleolar phenotype and increased rRNA levels. These data support a paradigm where soon after therapy release, the treated population mostly contains cells with a high level of widespread and catastrophic DNA damage that leads to apoptosis, while the minority of cells that have successful DDR are more likely to access a pro-survival state. These findings are consistent with accession of the polyaneuploid cancer cell (PACC) state, a recently described mechanism of therapy resistance and tumor recurrence. Our findings demonstrate the fate of cancer cells following cisplatin treatment and define key cell phenotypic characteristics of the PACC state. This work is essential for understanding and, ultimately, targeting cancer resistance and recurrence.
    Keywords:  Cancer therapy resistance; Nuclear morphology; Polyaneuploid cancer cell (PACC) state; Polyploidy
    DOI:  https://doi.org/10.1016/j.neo.2023.100906
  13. Cancers (Basel). 2023 May 07. pii: 2645. [Epub ahead of print]15(9):
    Osteocytes: New Kids on the Block for Cancer in Bone Therapy.
    Aric Anloague, Jesus Delgado-Calle.
      The tumor microenvironment plays a central role in the onset and progression of cancer in the bone. Cancer cells, either from tumors originating in the bone or from metastatic cancer cells from other body systems, are located in specialized niches where they interact with different cells of the bone marrow. These interactions transform the bone into an ideal niche for cancer cell migration, proliferation, and survival and cause an imbalance in bone homeostasis that severely affects the integrity of the skeleton. During the last decade, preclinical studies have identified new cellular mechanisms responsible for the dependency between cancer cells and bone cells. In this review, we focus on osteocytes, long-lived cells residing in the mineral matrix that have recently been identified as key players in the spread of cancer in bone. We highlight the most recent discoveries on how osteocytes support tumor growth and promote bone disease. Additionally, we discuss how the reciprocal crosstalk between osteocytes and cancer cells provides the opportunity to develop new therapeutic strategies to treat cancer in the bone.
    Keywords:  bone; breast cancer; cancer; metastasis; myeloma; osteocytes; sclerostin; therapy
    DOI:  https://doi.org/10.3390/cancers15092645
  14. Methods Mol Biol. 2023 ;2660 273-282
    Integrated In Silico Analysis of Proteogenomic and Drug Targets for Pancreatic Cancer Survival.
    Alakesh Bera, Digonto Chatterjee, Jack Hester, Meera Srivastava.
      Pancreatic cancer remains a major health concern, being among the deadliest forms of cancer with over 80% of the patients presenting with metastatic disease. According to the American Cancer Society, for all stages of pancreatic cancer combined, the 5-year survival rate is less than 10%. Genetic research on pancreatic cancer has generally been focused on familial pancreatic cancer, which is only 10% of all pancreatic cancer patients. This study focuses on finding genes that impact the survival of pancreatic cancer patients which can be used as biomarkers and potential targets to develop personalized treatment options. We used cBioPortal platform using NCI-initiated The Cancer Genome Atlas (TCGA) dataset to find genes that were altered differently in different ethnic groups which can serve as potential biomarkers and analyzed the genes' impact on patient survival. MD Anderson Cell Lines Project (MCLP) and genecards.org were also utilized to identify potential drug candidates that can target the proteins encoded by the genes. The results showed that there are unique genes that are associated with each race category which may influence the survival outcomes of patients, and their potential drug candidates were identified.
    Keywords:  Copy number alterations (CNAs); Disease-free survival (DFS); Drug targets; Genomics; MD Anderson Cell Lines Project (MCLP); Overall survival (OS); Pancreatic cancer; Proteogenomics; Proteomics; Socioeconomic status (SES); Survival outcomes; The Cancer Genome Atlas (TCGA); cBioPortal
    DOI:  https://doi.org/10.1007/978-1-0716-3163-8_19
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