Shadan Ali

Karmanos Cancer Institute, Detroit, Michigan, United States

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Publications (96)490.05 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Understanding of molecular events associated with tumor microenvironment in pancreatic cancer (PC) is an active area of research especially because of the rich desmoplasia seen in human PC. Desmoplasia is contributed by several cell types including cancer-associated fibroblast (CAF) and stellate cells (PSCs), which are believed to play critical roles in conferring aggressiveness to PC. The aberrant expression of microRNAs (miRNAs) in PSCs and CAF cells appears to play a pivotal role in the development and progression of PC. In this study, expression analysis of miR-21/miR-221 in conditioned media derived from PSCs/CAF cells, and from PSCs/CAF cells showed up-regulation of both miRNAs compared to MIAPaCa-2 PC cells. In addition, miR-21 expression in stellate cells derived from normal pancreas was substantially lower when compared to PSCs or CAF cells. COLO-357 PC cells cultured in the presence of conditioned media derived from PSC/CAF cells led to a significant increase in clonogenicity and pancreatosphere formation. Furthermore, inhibition of miR-21 with antisense oligonucleotide (ASO) transfection resulted in decreased migration/invasive capacity of PSCs. Similarly, the effect of ASO-miR-221 transfection in CAF cells reduced the expression of NF-κB and K-Ras (target of miR-221) along with inhibition of migration/invasion. Moreover, miRNA expression profiling of PSCs, MIAPaCa-2, and COLO-357 cells, and further validation by real-time PCR, showed several differentially expressed miRNAs, among which four was significantly up-regulated. Collectively, these results suggest a crosstalk between PSCs/CAF cells and PC cells, resulting in the up-regulation of miR-21/miR-221 expression which in part may confer aggressiveness to PC. We conclude that targeting these miRNAs could be useful for developing precision medicine for the prevention of tumor progression and/or for the treatment of PC.
    American Journal of Cancer Research 06/2015; 5(3):1251-64. · 4.17 Impact Factor

  • Cancer Research 10/2014; 74(19 Supplement):4351-4351. DOI:10.1158/1538-7445.AM2014-4351 · 9.33 Impact Factor

  • Cancer Research 10/2014; 74(19 Supplement):3552-3552. DOI:10.1158/1538-7445.AM2014-3552 · 9.33 Impact Factor

  • Cancer Research 10/2014; 74(19 Supplement):5589-5589. DOI:10.1158/1538-7445.AM2014-5589 · 9.33 Impact Factor
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    10/2014; 3(5):S5–S6. DOI:10.1016/j.jasc.2014.09.012
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    Bin Bao · Asfar S Azmi · Shadan Ali · Feras Zaiem · Fazlul H Sarkar ·
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    ABSTRACT: Metformin is one of the most used diabetic drugs for the management of type II diabetes mellitus (DM) in the world. Increased numbers of epidemiological and clinical studies have provided convincing evidence supporting the role of metformin in the development and progression of a variety of human tumors including breast and pancreatic cancer. Substantial pre-clinical evidence from in vitro and in vivo experimental studies strongly suggests that metformin has an anti-cancer activity mediated through the regulation of several cell signaling pathways including activation of AMP kinase (AMPK), and other direct and indirect mechanisms; however, the detailed mechanism(s) has not yet been fully understood. The concept of cancer stem cells (CSCs) has gained significant attention in recent years due its identification and defining its clinical implications in many different tumors including breast cancer and pancreatic cancer. In this review, we will discuss the protective role of metformin in the development of breast and pancreatic cancers. We will further discuss the role of metformin as an anti-cancer agent, which is in part mediated through targeting CSCs. Finally, we will discuss the potential role of metformin in the modulation of tumor-associated or CSC-associated microRNAs (miRNAs) as part of the novel mechanism of action of metformin in the development and progression of breast and pancreatic cancers.
    06/2014; 2(6):59. DOI:10.3978/j.issn.2305-5839.2014.06.05
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    ABSTRACT: Aberrant expression of microRNAs (miRNAs) plays important roles in the development and progression of pancreatic cancer (PC). Expression analysis of miR-146a in human PC tissues showed decreased expression in about 80% of samples compared to corresponding non-cancerous tissue. Moreover, expression of miR-146a in eight PC cell lines, and in pancreatic tissues obtained from transgenic mouse models of K-Ras (K), Pdx1-Cre (C), K-Ras;Pdx1-Cre (KC) and K-Ras;Pdx1-Cre;INK4a/Arf (KCI), showed down-regulation of miR-146a expression in KCI mice which was in part led to over-expression of its target gene, epidermal growth factor receptor (EGFR). Treatment of PC cells with CDF, a novel synthetic compound, led to re-expression of miR-146a, resulting in the down-regulation of EGFR expression. Moreover, re-expression of miR-146a by stable transfection or treatment with CDF in vivo (xenograft animal model) resulted in decreased tumor growth which was consistent with reduced EGFR, ERK1, ERK2, and K-Ras expression. Further knock-down of miR-146a in AsPC-1 cells led to the up-regulation of EGFR expression and showed increased clonogenic growth. In addition, knock-down of EGFR by EGFR siRNA transfection of parental AsPC-1 cells and AsPC-1 cells stably transfected with pre-miR-146a resulted in decreased invasive capacity, which was further confirmed by reduced luciferase activity in cells transfected with pMIR-Luc reporter vector containing miR-146a binding site. Collectively, these results suggest that the loss of expression of miR-146a is a fundamental mechanism for over-expression of EGFR signaling and that re-expression of miR-146a by CDF treatment could be useful in designing personalized strategy for the treatment of human PC.
    Cancer Letters 05/2014; 351(1). DOI:10.1016/j.canlet.2014.05.013 · 5.62 Impact Factor
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    ABSTRACT: Pancreatic cancer (PC) is one of the most deadly cancers. The higher mortality is in part due to treatment resistance and early onset of metastasis. The existence of cancer stem like cells (CSLCs) has been widely accepted to be responsible for tumor aggressiveness in PC. Emerging evidence suggests that CSLCs have the capacity for increased cell growth, cell migration/invasion, metastasis, and treatment resistance, which leads to poor clinical outcome. However, the molecular role of CSLCs in tumor development and progression is poorly understood. Therefore, mechanistic understanding, and targeted killing of CSLCs may provide a newer therapeutic strategy for the treatment of PC. It has been well accepted that microRNAs (miRNAs) play critical roles during tumor development and progression through deregulation of multiple genes. Moreover, deregulated expression of miRNAs may also play a key role in the regulation of CSLCs characteristics and functions. Here we show that isolated CD44+/CD133+/EpCAM+ cells (triple-positive cells) from human PC cell lines, MiaPaCa-2 and L3.6pl cells display aggressive characteristics such as increased cell growth, clonogenicity, cell migration, and self-renewal capacity, which is consistent with over-expression of CSLC signatures/markers. We also found deregulated expression of over 400 miRNAs including let-7, miR-30, miR-125b, and miR-335 in CSLCs. As a proof-of-concept, knockdown of miR-125b resulted in the inhibition of tumor cell aggressiveness of CSLCs (triple-positive cells), consistent with the down-regulation of CD44, EpCAM, EZH2, and snail. These results clearly suggest the importance of miRNAs in the regulation of CSLCs characteristics, and may serve as novel targets for therapy.
    Stem cells and development 04/2014; 23(16). DOI:10.1089/scd.2013.0551 · 3.73 Impact Factor
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    ABSTRACT: Sub-populations of cancer stem cells (CSCs) or cancer stem-like cells (CSLCs) have been identified from most tumors including pancreatic cancer (PC), and the existence of these cells is clinically relevant. Emerging evidence suggests that CSLCs participate in cell growth/proliferation, migration/invasion, metastasis, and chemo-radio-therapy resistance, ultimately contributing to poor clinical outcome. However, the pathogenesis and biological significance of CSLCs in PC has not been well characterized. In the present study, we found that isolated triple-marker positive (CD44+/CD133+/EpCAM+) cells of human PC MiaPaCa-2 and L3.6pl cells behave as CSLCs. These CSLCs exhibit aggressive behavior such as increased cell growth, migration, clonogenicity, and self-renewal capacity. The mRNA expression profiling analysis showed that CSLCs (CD44+/CD133+/EpCAM+) exhibit differential expression of more than 1600 mRNAs including FoxQ1, compared to the triple-marker negative (CD44-/CD133-/EpCAM-) cells. The knock-down of FoxQ1 by its siRNA in CSLCs resulted in the inhibition of aggressive behavior, consistent with the inhibition of EpCAM and snail expression. Mouse xenograft tumor studies showed that CSLCs have a 100-fold higher potential for tumor formation and rapid tumor growth, consistent with over-expression of CSC-associated markers/mediators including FoxQ1, compared to its parental MiaPaCa-2 cells. The inhibition of FoxQ1 attenuated tumor formation and growth, and expression of CSC markers in the xenograft tumor derived from CSLCs of MiaPaCa-2 cells. These data clearly suggesting the role of differentially expressed genes in the regulation of CSLC characteristics, further suggesting that targeting some of these genes could be important for the development of novel therapies for achieving better treatment outcome of PC.
    Journal of Biological Chemistry 04/2014; 289(21). DOI:10.1074/jbc.M113.532887 · 4.57 Impact Factor
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    ABSTRACT: Pancreatic cancer (PC) is a lethal malignant disease, which is in part due to lack of early detection biomarkers. Once diagnosed, the majority of PC patients are already in advanced stages. Currently there are no effective treatments in improving the overall survival. Therefore, the majority of PC patients die within 5-6 months due to therapeutic resistance and early metastatic disease. Recently, a sub-population of cancer stem cells (CSCs) (<0.1%) have been identified from many different tumors including PC, and these cells are believed to be responsible for treatment resistance, tumor recurrence and metastasis. Many studies have shown that the existence of CSCs has important clinical implications because CSCs are involved in cell migration/invasion, drug resistance, and metastasis, which leads to poor clinical outcome. Therefore, selective killing or complete elimination of CSCs by novel approaches would likely become newer treatment strategy for PC in the improvement of overall survival. However, the regulation of CSC characteristics during tumor development and progression has not been well understood. In this study, cell and molecular biology techniques were used to investigate the CSC characteristics and its regulation to find a new effective approach for the treatment of PC. We found that cancer stem-like cells (CSLCs) which is reminiscent of CSCs isolated from human PC cell line, MiaPaCa-2 cells as triple-marker positive cells (CD44+/CD133+/EpCAM+ cells) cells displayed aggressive phenotypes, such as increased clonogenicity, cell migration, and self-renewal capacity, along with over-expression of CSC marker microRNAs (miRNAs) such as miR-21 and miR-210. Under-expression of miR-21 and miR-210 by transfection of anti-miRNAs led to decreased clonogenicity, cell migration and self-renewal capacity, along with reduced expression of CSC-associated markers/mediators such as CD44, EpCAM, EZH2, Notch-1, and Snail in CSLCs. Similarly, under-expression of CSC-associated mediator Notch-1 led to decreased cell migration, self-renewal capacity, and expression of EpCAM and Snail in CSLCs. Finally, CDF, a novel synthetic small molecule showed reduced aggressive behavior of CSLCs such as cell survival/growth, migration, clonogenicity, self-renewal capacity, and decreased expression of miR-21 and miR-210. From these results, we conclude that CDF may serve as an effective anti-tumor agent via targeting miRNA-driven aggressive behavior of CSLCs.
    American Association for Cancer Research; 04/2014
  • Alia Ahmed · Shadan Ali · Fazlul H Sarkar ·
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    ABSTRACT: Prostate Cancer (PCa) is the second leading cause of cancer death in men. Current research findings suggest that the androgen receptor (AR) and its signaling pathway contribute significantly to the progression of metastatic PCa. The AR is a ligand activated transcription factor, where androgens such as testosterone (T) and dihydroxytestosterone (DHT) act as the activating ligands. However in many metastatic PCa, the AR functions promiscuously and is constitutively active through multiple mechanisms. Inhibition of enzymes that take part in androgen synthesis or synthesizing antiandrogens that can inhibit the AR are two popular methods of impeding the androgen receptor signaling axis; however, the inhibition of androgen-independent activated AR function has not yet been fully exploited. This article focuses on the development of emerging novel agents that act at different steps along the androgen-AR signaling pathway to help improve the poor prognosis of PCa patients. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.
    Journal of Cellular Physiology 03/2014; 229(3). DOI:10.1002/jcp.24456 · 3.84 Impact Factor
  • Seema Sethi · Shadan Ali · Sajiv Sethi · Fazlul. H. Sarkar ·
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    ABSTRACT: MicroRNAs (miRNAs) are small endogenous non-coding single-stranded RNAs. They critically regulate the post-transcriptional activity of several key physiological and pathological cell processes including cancer. Through their transcriptional regulatory functions, miRNAs control tumor proliferation, invasion and metastasis. The expression of miRNAs is altered in malignancies. It could be either up or down-regulated depending upon the role of a particular miRNA in the pathogenetic development of the tumor. The up-regulated miRNAs exert an ‘oncogenic’ effect leading to tumor proliferation and metastasis. The down-regulated miRNAs have ‘tumor suppressor’ effects. Recent studies have demonstrated that miRNAs have a role in the early diagnosis, prognosis and treatment outcome assessment of cancers. Every tumor has specific miRNA alterations i.e. some are over expressed and others are down-regulated. These altered miRNAs can be used as a tumor specific 'signature' for potential clinical use in improving accuracy of diagnosis, determining prognosis and as therapeutic targets for therapy. Specific miRNAs can be targeted using oligonucleotide sequences corresponding to the altered miRNAs. These are referred to as ‘antagomirs’. Depending upon the miRNA alterations in the tumor of an individual patient, one could design targeted therapies for personalized medicine in patients. Hence miRNAs have an immense role in personalized cancer therapy.
    Clinical Genetics 02/2014; 86(1). DOI:10.1111/cge.12362 · 3.93 Impact Factor
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    ABSTRACT: The concept of cancer stem cells (CSCs) has great clinical implications because small sub-populations of CSCs have been identified in many different tumors that are associated with poor clinical outcome. Sufficient evidence supports central functions of CSCs in tumorigenesis, due to its distinct high potentials of self-renewal, pluripotent differentiation and apoptosis-resistance, contributing to tumor aggressiveness. Therefore, inhibiting/eliminating CSCs will provide a new effective therapeutic approach for the treatment of aggressive tumors. However, the mechanistic roles of CSCs in tumorigenesis are not well understood. MicroRNAs (miRNAs) have been discovered to act as key regulators of gene expression in tumorigenesis. Aberrant expression of miRNAs has been discovered to be related to worse clinical outcome of many different tumors. Evidence shows that these tumor-related miRNAs have key functions in the regulation of cell cycle/proliferation, migration/invasion, chemo-radiation resistance, and metastasis. Moreover, miRNAs may also exert important functions in modulating CSC characteristics; however, its detailed mechanism(s) has not been fully elucidated. Here, we will summarize the potential role of CSC-related miRNAs in CSC function, and will further define the role of genistein in targeting these CSC-related miRNAs.
    MicroRNAs: Key Regulators of Oncogenesis, 01/2014: pages 295-320; , ISBN: 978-3-319-03724-0
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    ABSTRACT: MicroRNAs are small endogenous noncoding RNAs that are critical regulators of several physiologic and pathologic processes including cancers. Variations in the level of microRNA expression have been linked with the development, progression, and spread of cancer to distant organs. These tiny molecules may play a role in accurate and early diagnosis, and also as prognostic determinants. Modulating their activity provides opportunities for developing and designing novel cancer therapeutics. Recent studies indicate their detection in a wide variety of human biologic specimens including blood, serum, fine-needle aspirates, and tissues, making them clinically useful biomarkers of disease for early detection, prognosis, and for designing personalized therapies.
    Clinics in laboratory medicine 12/2013; 33(4):773-786. DOI:10.1016/j.cll.2013.08.001 · 1.37 Impact Factor
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    ABSTRACT: Pancreatic cancer is the fourth leading cause of cancer related death in the US and exhibits aggressive features with short survival rate and high mortality. Therefore, it is important to understand the molecular mechanism(s) involved in the aggressive growth of pancreatic cancers, and further design novel targeted therapies for its treatment with better treatment outcome. In the present study, we found that the expression of miR-221 was significantly up-regulated in pancreatic cancer cell lines and tumor tissues compared to normal pancreatic duct epithelial cells and normal pancreas tissues. Moreover, we found that the pancreatic cancer patients with high miR-221 expression had a relatively shorter survival compared to those with lower expression, suggesting that miR-221 could be an oncogenic miRNA and a prognostic factor for poor survival of patients. Interestingly, transfection of miR-221 inhibitor suppressed the proliferative capacity of pancreatic cancer cells with concomitant up-regulation of PTEN, p27(kip1), p57(kip2), and PUMA, which are the tumor suppressors and the predicted targets of miR-221. Most importantly, we found that the treatment of pancreatic cancer cells with isoflavone mixture (G2535), formulated 3,3'-diindolylmethane (BR-DIM), or synthetic curcumin analogue (CDF) could down-regulate the expression of miR-221 and consequently up-regulate the expression of PTEN, p27(kip1), p57(kip2), and PUMA, leading to the inhibition of cell proliferation and migration of MiaPaCa-2 and Panc-1 cells. These results provide experimental evidence in support of the oncogenic role of miR-221 and also demonstrate the role of isoflavone, BR-DIM, and CDF as potential non-toxic agents that are capable of down-regulation of miR-221. Therefore, these agents combined with conventional chemotherapeutics could be useful in designing novel targeted therapeutic strategy for the treatment of pancreatic cancer for which there is no curative therapy.
    American Journal of Cancer Research 11/2013; 3(5):465-77. · 4.17 Impact Factor
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    ABSTRACT: Reactive oxygen species (ROS) have been widely considered as critical cellular signaling molecules involving in various biological processes such as cell growth, differentiation, proliferation, apoptosis, and angiogenesis. The homeostasis of ROS is critical to maintain normal biological processes. Increased production of ROS, namely oxidative stress, due to either endogenous or exogenous sources causes irreversible damage of bio-molecules such as DNA, proteins, lipids, and sugars, leading to genomic instability, genetic mutation, and altered gene expression, eventually contributing to tumorigenesis. A great amount of experimental studies in vitro and in vivo have produced solid evidence supporting that oxidative stress is strongly associated with increased tumor cell growth, treatment resistance, and metastasis, and all of which contribute to tumor aggressiveness. More recently, the data have indicated that altered production of ROS is also associated with cancer stem cells (CSCs), epithelial-to-mesenchymal transition (EMT), and hypoxia, the most common features or phenomena in tumorigenesis and tumor progression. However, the exact mechanism by which ROS is involved in the regulation of CSC and EMT characteristics as well as hypoxia- and, especially, HIF-mediated pathways is not well known. Emerging evidence suggests the role of miRNAs in tumorigenesis and progression of human tumors. Recently, the data have indicated that altered productions of ROS are associated with deregulated expression of miRNAs, suggesting their potential roles in the regulation of ROS production. Therefore, targeting ROS mediated through the deregulation of miRNAs by novel approaches or by naturally occurring anti-oxidant agents such as genistein could provide a new therapeutic approach for the prevention and/or treatment of human malignancies.
    Current Stem Cell Research & Therapy 08/2013; 9(1). DOI:10.2174/1574888X113089990053 · 2.21 Impact Factor
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    ABSTRACT: Isoflavones have been investigated in detail for their role in the prevention and therapy of prostate cancer. This is primarily because of the overwhelming data connecting high dietary isoflavone intake with reduced risk of developing prostate cancer. A number of investigations have evaluated the mechanism(s) of anticancer action of isoflavones such as genistein, daidzein, biochanin A, equol, etc., in various prostate cancer models, both in vitro and in vivo. Genistein quickly jumped to the forefront of isoflavone cancer research, but the initial enthusiasm was followed by reports on its contradictory prometastatic and tumor-promoting effects. Use of soy isoflavone mixture has been advocated as an alternative, wherein daidzein can negate harmful effects of genistein. Recent research indicates a novel role of genistein and other isoflavones in the potentiation of radiation therapy, epigenetic regulation of key tumor suppressors and oncogenes, and the modulation of miRNAs, epithelial-to-mesenchymal transition, and cancer stem cells, which has renewed the interest of cancer researchers in this class of anticancer compounds. This comprehensive review article summarizes our current understanding of the role of isoflavones in prostate cancer research.
    The AAPS Journal 07/2013; 15(4). DOI:10.1208/s12248-013-9507-1 · 3.80 Impact Factor
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    ABSTRACT: Cancer diagnosis is currently undergoing a paradigm shift with the incorporation of molecular biomarkers as part of routine diagnostic panel. The molecular alteration ranges from those involving the DNA, RNA, microRNAs (miRNAs) and proteins. The miRNAs are recently discovered small non-coding endogenous single-stranded RNAs that critically regulates the development, invasion and metastasis of cancers. They are altered in cancers and have the potential to serve as diagnostic markers for cancer. Moreover, deregulating their activity offers novel cancer therapeutic approaches. The availability of high throughput techniques for the identification of altered cellular molecules allowed their use in cancer diagnosis. Their application to a variety of body specimens from blood to tissues has been helpful for appreciating their use in the clinical context. The development of innovative antibodies for immunohistochemical detection of proteins also assists in diagnosis and risk stratification. Overall, the novel cancer diagnostic tools have extended their application as prognostic risk factors and can be used as targets for personalized medicine.
    International Journal of Molecular Sciences 07/2013; 14(7):14771-84. DOI:10.3390/ijms140714771 · 2.86 Impact Factor
  • Bin Bao · Aamir Ahmad · Asfar S Azmi · Shadan Ali · Fazlul H Sarkar ·
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    ABSTRACT: The identification of small subpopulations of cancer stem cells (CSCs) from blood mononuclear cells in human acute myeloid leukemia (AML) in 1997 was a landmark observation that recognized the potential role of CSCs in tumor aggressiveness. Two critical properties contribute to the functional role of CSCs in the establishment and recurrence of cancerous tumors: their capacity for self-renewal and their potential to differentiate into unlimited heterogeneous populations of cancer cells. These findings suggest that CSCs may represent novel therapeutic targets for the treatment and/or prevention of tumor progression, since they appear to be involved in cell migration, invasion, metastasis, and treatment resistance-all of which lead to poor clinical outcomes. The identification of CSC-specific markers, the isolation and characterization of CSCs from malignant tissues, and targeting strategies for the destruction of CSCs provide a novel opportunity for cancer research. This overview describes the potential implications of several common CSC markers in the identification of CSC subpopulations that are restricted to common malignant diseases, e.g., leukemia, and breast, prostate, pancreatic, and lung cancers. The role of microRNAs (miRNAs) in the regulation of CSC function is also discussed, as are several methods commonly used in CSC research. The potential role of the antidiabetic drug metformin- which has been shown to have effects on CSCs, and is known to function as an antitumor agent-is discussed as an example of this new class of chemotherapeutics.Curr. Protoc. Pharmacol. 61:14.25.1-14.25.14 © 2013 by John Wiley & Sons, Inc.
    Current protocols in pharmacology 06/2013; Chapter 14:Unit14.25. DOI:10.1002/0471141755.ph1425s61
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    ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most frequently diagnosed cancers and the fourth leading cause of cancer-related death in the United States, suggesting that there is an urgent need to design novel strategies for achieving better treatment outcome of patients diagnosed with PDAC. Our previous study has shown that activation of Notch and NF-κB play a critical role in the development of PDAC in the compound K-Ras(G12D) and Ink4a/Arf deficient transgenic mice. However, the exact molecular mechanism by which mutated K-Ras and Ink4a/Arf deficiency contribute to progression of PDAC remains largely elusive. In the present study, we used multiple methods, such as Real-time RT-PCR, Western blotting assay and immunohistochemistry to gain further mechanistic insight. We found that the deletion of Ink4a/Arf in K-Ras(G12D) expressing mice led to high expression of PDGF-D signaling pathway in the tumor and tumor-derived cell line (RInk-1 cells). Furthermore, PDGF-D knock-down in RInk-1 cells resulted in the inhibition of pancreatosphere formation and down-regulation of EZH2, CD44, EpCAM, and vimentin. Moreover, we demonstrated that epithelial-mesenchymal transition (EMT) was induced in the compound mice, which is linked with aggressiveness of PDAC. In addition, we demonstrated that tumors from compound transgenic mice have higher expression of cancer stem cell (CSC) markers. These results suggest that the acquisition of EMT phenotype and induction of CSC characteristics could be linked with the aggressiveness of PDAC mediated in part through the activation of PDGF-D, signaling. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.
    Journal of Cellular Physiology 03/2013; 228(3). DOI:10.1002/jcp.24162 · 3.84 Impact Factor

Publication Stats

4k Citations
490.05 Total Impact Points


  • 2003-2015
    • Karmanos Cancer Institute
      • Division of Hematology and Oncology
      Detroit, Michigan, United States
  • 2007-2014
    • Wayne State University
      • • Department of Pathology
      • • Department of Internal Medicine
      • • Division of Hematology and Oncology
      Detroit, Michigan, United States