Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018, 68(6):394-424.
Pancreatic Cancer: Statistics [https://www.cancer.net/cancer-types/pancreatic-cancer/statistics]
Apte MV, Park S, Phillips PA, Santucci N, Goldstein D, Kumar RK, Ramm GA, Buchler M, Friess H, McCarroll JA et al: Desmoplastic reaction in pancreatic cancer: role of pancreatic stellate cells. Pancreas 2004, 29(3):179-187.
Bachem MG, Schunemann M, Ramadani M, Siech M, Beger H, Buck A, Zhou S, Schmid-Kotsas A, Adler G: Pancreatic carcinoma cells induce fibrosis by stimulating proliferation and matrix synthesis of stellate cells. Gastroenterology 2005, 128(4):907-921.
Kota J, Hancock J, Kwon J, Korc M: Pancreatic cancer: Stroma and its current and emerging targeted therapies. Cancer Lett 2017, 391:38-49.
Apte MV, Pirola RC, Wilson JS: Pancreatic stellate cells: a starring role in normal and diseased pancreas. Front Physiol 2012, 3:344.
Bachem MG, Schneider E, Gross H, Weidenbach H, Schmid RM, Menke A, Siech M, Beger H, Grunert A, Adler G: Identification, culture, and characterization of pancreatic stellate cells in rats and humans. Gastroenterology 1998, 115(2):421-432.
Masamune A, Watanabe T, Kikuta K, Shimosegawa T: Roles of pancreatic stellate cells in pancreatic inflammation and fibrosis. Clin Gastroenterol Hepatol 2009, 7(11 Suppl):S48-54.
Farran B, Nagaraju GP: The dynamic interactions between the stroma, pancreatic stellate cells and pancreatic tumor development: Novel therapeutic targets. Cytokine Growth Factor Rev 2019, 48:11-23.
Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116(2):281-297.
Fabian MR, Sonenberg N, Filipowicz W: Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 2010, 79:351-379.
Macfarlane LA, Murphy PR: MicroRNA: Biogenesis, Function and Role in Cancer. Curr Genomics 2010, 11(7):537-561.
Couzin J: MicroRNAs make big impression in disease after disease. Science 2008, 319(5871):1782-1784.
Rupaimoole R, Slack FJ: MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 2017, 16(3):203-222.
Kadera BE, Li L, Toste PA, Wu N, Adams C, Dawson DW, Donahue TR: MicroRNA-21 in pancreatic ductal adenocarcinoma tumor-associated fibroblasts promotes metastasis. PLoS One 2013, 8(8):e71978.
Ali S, Suresh R, Banerjee S, Bao B, Xu Z, Wilson J, Philip PA, Apte M, Sarkar FH: Contribution of microRNAs in understanding the pancreatic tumor microenvironment involving cancer associated stellate and fibroblast cells. Am J Cancer Res 2015, 5(3):1251-1264.
Kim JE, Kim BG, Jang Y, Kang S, Lee JH, Cho NH: The stromal loss of miR-4516 promotes the FOSL1-dependent proliferation and malignancy of triple negative breast cancer. Cancer Lett 2020, 469:256-265.
Qin X, Guo H, Wang X, Zhu X, Yan M, Wang X, Xu Q, Shi J, Lu E, Chen W et al: Exosomal miR-196a derived from cancer-associated fibroblasts confers cisplatin resistance in head and neck cancer through targeting CDKN1B and ING5. Genome Biol 2019, 20(1):12.
Taddei ML, Cavallini L, Ramazzotti M, Comito G, Pietrovito L, Morandi A, Giannoni E, Raugei G, Chiarugi P: Stromal-induced downregulation of miR-1247 promotes prostate cancer malignancy. J Cell Physiol 2019, 234(6):8274-8285.
Eichelmann AK, Matuszcak C, Hummel R, Haier J: Role of miRNAs in cell signaling of cancer associated fibroblasts. Int J Biochem Cell Biol 2018, 101:94-102.
Kwon JJ, Nabinger SC, Vega Z, Sahu SS, Alluri RK, Abdul-Sater Z, Yu Z, Gore J, Nalepa G, Saxena R et al: Pathophysiological role of microRNA-29 in pancreatic cancer stroma. Sci Rep 2015, 5:11450.
FastQC: A Quality Control Tool for High Throughput Sequence Data [Online] [http://www.bioinformatics.babraham.ac.uk/projects/fastqc/]
Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR: STAR: ultrafast universal RNA-seq aligner. Bioinformatics 2013, 29(1):15-21.
Liao Y, Smyth GK, Shi W: featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 2014, 30(7):923-930.
Jensen LJ, Kuhn M, Stark M, Chaffron S, Creevey C, Muller J, Doerks T, Julien P, Roth A, Simonovic M et al: STRING 8--a global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Res 2009, 37(Database issue):D412-416.
Hamidi H, Pietila M, Ivaska J: The complexity of integrins in cancer and new scopes for therapeutic targeting. Br J Cancer 2016, 115(9):1017-1023.
Kesteloot F, Desmouliere A, Leclercq I, Thiry M, Arrese JE, Prockop DJ, Lapiere CM, Nusgens BV, Colige A: ADAM metallopeptidase with thrombospondin type 1 motif 2 inactivation reduces the extent and stability of carbon tetrachloride-induced hepatic fibrosis in mice. Hepatology 2007, 46(5):1620-1631.
Wang X, Chen W, Zhang J, Khan A, Li L, Huang F, Qiu Z, Wang L, Chen X: Critical Role of ADAMTS2 (A Disintegrin and Metalloproteinase With Thrombospondin Motifs 2) in Cardiac Hypertrophy Induced by Pressure Overload. Hypertension 2017, 69(6):1060-1069.
Bekhouche M, Leduc C, Dupont L, Janssen L, Delolme F, Vadon-Le Goff S, Smargiasso N, Baiwir D, Mazzucchelli G, Zanella-Cleon I et al: Determination of the substrate repertoire of ADAMTS2, 3, and 14 significantly broadens their functions and identifies extracellular matrix organization and TGF-beta signaling as primary targets. FASEB J 2016, 30(5):1741-1756.
Hung CF, Rohani MG, Lee SS, Chen P, Schnapp LM: Role of IGF-1 pathway in lung fibroblast activation. Respir Res 2013, 14:102.
Adamek A, Kasprzak A: Insulin-Like Growth Factor (IGF) System in Liver Diseases. Int J Mol Sci 2018, 19(5).
Svegliati-Baroni G, Ridolfi F, Di Sario A, Casini A, Marucci L, Gaggiotti G, Orlandoni P, Macarri G, Perego L, Benedetti A et al: Insulin and insulin-like growth factor-1 stimulate proliferation and type I collagen accumulation by human hepatic stellate cells: differential effects on signal transduction pathways. Hepatology 1999, 29(6):1743-1751.
Mutgan AC, Besikcioglu HE, Wang S, Friess H, Ceyhan GO, Demir IE: Insulin/IGF-driven cancer cell-stroma crosstalk as a novel therapeutic target in pancreatic cancer. Mol Cancer 2018, 17(1):66.
Li ZH, Xiong QY, Xu L, Duan P, Yang QO, Zhou P, Tu JH: miR-29a regulated ER-positive breast cancer cell growth and invasion and is involved in the insulin signaling pathway. Oncotarget 2017, 8(20):32566-32575.
Yang J, Waldron RT, Su HY, Moro A, Chang HH, Eibl G, Ferreri K, Kandeel FR, Lugea A, Li L et al: Insulin promotes proliferation and fibrosing responses in activated pancreatic stellate cells. Am J Physiol Gastrointest Liver Physiol 2016, 311(4):G675-G687.
Hastings JF, Skhinas JN, Fey D, Croucher DR, Cox TR: The extracellular matrix as a key regulator of intracellular signalling networks. Br J Pharmacol 2019, 176(1):82-92.
Hakuno F, Takahashi SI: IGF1 receptor signaling pathways. J Mol Endocrinol 2018, 61(1):T69-T86.
Braicu C, Buse M, Busuioc C, Drula R, Gulei D, Raduly L, Rusu A, Irimie A, Atanasov AG, Slaby O et al: A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer. Cancers (Basel) 2019, 11(10).
Dey S, Kwon JJ, Liu S, Hodge GA, Taleb S, Zimmers TA, Wan J, Kota J: miR-29a Is Repressed by MYC in Pancreatic Cancer and Its Restoration Drives Tumor-Suppressive Effects via Downregulation of LOXL2. Mol Cancer Res 2020, 18(2):311-323.
Pandol S, Edderkaoui M, Gukovsky I, Lugea A, Gukovskaya A: Desmoplasia of pancreatic ductal adenocarcinoma. Clin Gastroenterol Hepatol 2009, 7(11 Suppl):S44-47.
Viloria K, Munasinghe A, Asher S, Bogyere R, Jones L, Hill NJ: A holistic approach to dissecting SPARC family protein complexity reveals FSTL-1 as an inhibitor of pancreatic cancer cell growth. Sci Rep 2016, 6:37839.
Jang I, Beningo KA: Integrins, CAFs and Mechanical Forces in the Progression of Cancer. Cancers (Basel) 2019, 11(5).
Aumailley M: The laminin family. Cell Adh Migr 2013, 7(1):48-55.
Givant-Horwitz V, Davidson B, Reich R: Laminin-induced signaling in tumor cells. Cancer Lett 2005, 223(1):1-10.
Nishikawa R, Goto Y, Kojima S, Enokida H, Chiyomaru T, Kinoshita T, Sakamoto S, Fuse M, Nakagawa M, Naya Y et al: Tumor-suppressive microRNA-29s inhibit cancer cell migration and invasion via targeting LAMC1 in prostate cancer. Int J Oncol 2014, 45(1):401-410.
Kashima H, Wu RC, Wang Y, Sinno AK, Miyamoto T, Shiozawa T, Wang TL, Fader AN, Shih Ie M: Laminin C1 expression by uterine carcinoma cells is associated with tumor progression. Gynecol Oncol 2015, 139(2):338-344.
Zhang Y, Xi S, Chen J, Zhou D, Gao H, Zhou Z, Xu L, Chen M: Overexpression of LAMC1 predicts poor prognosis and enhances tumor cell invasion and migration in hepatocellular carcinoma. J Cancer 2017, 8(15):2992-3000.
Takahashi S, Hasebe T, Oda T, Sasaki S, Kinoshita T, Konishi M, Ochiai T, Ochiai A: Cytoplasmic expression of laminin gamma2 chain correlates with postoperative hepatic metastasis and poor prognosis in patients with pancreatic ductal adenocarcinoma. Cancer 2002, 94(6):1894-1901.
Miyamoto H, Murakami T, Tsuchida K, Sugino H, Miyake H, Tashiro S: Tumor-stroma interaction of human pancreatic cancer: acquired resistance to anticancer drugs and proliferation regulation is dependent on extracellular matrix proteins. Pancreas 2004, 28(1):38-44.
Damiano JS, Cress AE, Hazlehurst LA, Shtil AA, Dalton WS: Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood 1999, 93(5):1658-1667.
Zhang H, Ozaki I, Mizuta T, Matsuhashi S, Yoshimura T, Hisatomi A, Tadano J, Sakai T, Yamamoto K: Beta 1-integrin protects hepatoma cells from chemotherapy induced apoptosis via a mitogen-activated protein kinase dependent pathway. Cancer 2002, 95(4):896-906.
Amrutkar M, Aasrum M, Verbeke CS, Gladhaug IP: Secretion of fibronectin by human pancreatic stellate cells promotes chemoresistance to gemcitabine in pancreatic cancer cells. BMC Cancer 2019, 19(1):596.
Rucki AA, Foley K, Zhang P, Xiao Q, Kleponis J, Wu AA, Sharma R, Mo G, Liu A, Van Eyk J et al: Heterogeneous Stromal Signaling within the Tumor Microenvironment Controls the Metastasis of Pancreatic Cancer. Cancer Res 2017, 77(1):41-52.
Rohrmann S, Grote VA, Becker S, Rinaldi S, Tjonneland A, Roswall N, Gronbaek H, Overvad K, Boutron-Ruault MC, Clavel-Chapelon F et al: Concentrations of IGF-I and IGFBP-3 and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. Br J Cancer 2012, 106(5):1004-1010.
Sobel G, Szabo I, Paska C, Kiss A, Kovalszky I, Kadar A, Paulin F, Schaff Z: Changes of cell adhesion and extracellular matrix (ECM) components in cervical intraepithelial neoplasia. Pathol Oncol Res 2005, 11(1):26-31.
Huang J, Zhang L, He C, Qu Y, Li J, Zhang J, Du T, Chen X, Yu Y, Liu B et al: Claudin-1 enhances tumor proliferation and metastasis by regulating cell anoikis in gastric cancer. Oncotarget 2015, 6(3):1652-1665.
Wu X, Xiao J, Zhao C, Zhao C, Han Z, Wang F, Yang Y, Jiang Y, Fang F: Claudin1 promotes the proliferation, invasion and migration of nasopharyngeal carcinoma cells by upregulating the expression and nuclear entry of beta-catenin. Exp Ther Med 2018, 16(4):3445-3451.
Xue R, Hua L, Xu W, Gao Y, Pang Y, Hao J: Derivation and Validation of the Potential Core Genes in Pancreatic Cancer for Tumor-Stroma Crosstalk. Biomed Res Int 2018, 2018:4283673.
Hatakeyama N, Kojima T, Iba K, Murata M, Thi MM, Spray DC, Osanai M, Chiba H, Ishiai S, Yamashita T et al: IGF-I regulates tight-junction protein claudin-1 during differentiation of osteoblast-like MC3T3-E1 cells via a MAP-kinase pathway. Cell Tissue Res 2008, 334(2):243-254.
Lara-Diaz VJ, Castilla-Cortazar I, Martin-Estal I, Garcia-Magarino M, Aguirre GA, Puche JE, de la Garza RG, Morales LA, Munoz U: IGF-1 modulates gene expression of proteins involved in inflammation, cytoskeleton, and liver architecture. J Physiol Biochem 2017, 73(2):245-258.
Roderburg C, Luedde M, Vargas Cardenas D, Vucur M, Mollnow T, Zimmermann HW, Koch A, Hellerbrand C, Weiskirchen R, Frey N et al: miR-133a mediates TGF-beta-dependent derepression of collagen synthesis in hepatic stellate cells during liver fibrosis. J Hepatol 2013, 58(4):736-742.
Huang G, Ge G, Izzi V, Greenspan DS: alpha3 Chains of type V collagen regulate breast tumour growth via glypican-1. Nat Commun 2017, 8:14351.
Weniger M, Honselmann KC, Liss AS: The Extracellular Matrix and Pancreatic Cancer: A Complex Relationship. Cancers (Basel) 2018, 10(9).
Saneyasu T, Akhtar R, Sakai T: Molecular Cues Guiding Matrix Stiffness in Liver Fibrosis. Biomed Res Int 2016, 2016:2646212.
Hazar-Rethinam M, de Long LM, Gannon OM, Boros S, Vargas AC, Dzienis M, Mukhopadhyay P, Saenz-Ponce N, Dantzic DD, Simpson F et al: RacGAP1 Is a Novel Downstream Effector of E2F7-Dependent Resistance to Doxorubicin and Is Prognostic for Overall Survival in Squamous Cell Carcinoma. Mol Cancer Ther 2015, 14(8):1939-1950.
Lomberk G, Blum Y, Nicolle R, Nair A, Gaonkar KS, Marisa L, Mathison A, Sun Z, Yan H, Elarouci N et al: Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes. Nat Commun 2018, 9(1):1978.
Wang Y: The effect of E2F7 expression in prostate cancer on apoptosis and cell cycle of prostate cancer cells. Journal of Clinical Oncology 2019, 37(15_suppl):e16568-e16568.
Carvajal LA, Hamard PJ, Tonnessen C, Manfredi JJ: E2F7, a novel target, is up-regulated by p53 and mediates DNA damage-dependent transcriptional repression. Genes Dev 2012, 26(14):1533-1545.
Musa J, Aynaud MM, Mirabeau O, Delattre O, Grunewald TG: MYBL2 (B-Myb): a central regulator of cell proliferation, cell survival and differentiation involved in tumorigenesis. Cell Death Dis 2017, 8(6):e2895.
Qin H, Li Y, Zhang H, Wang F, He H, Bai X, Li S: Prognostic implications and oncogenic roles of MYBL2 protein expression in esophageal squamous-cell carcinoma. Onco Targets Ther 2019, 12:1917-1927.
Bhardwaj A, Srivastava SK, Singh S, Tyagi N, Arora S, Carter JE, Khushman M, Singh AP: MYB Promotes Desmoplasia in Pancreatic Cancer through Direct Transcriptional Up-regulation and Cooperative Action of Sonic Hedgehog and Adrenomedullin. J Biol Chem 2016, 291(31):16263-16270.
Saison-Ridinger M, DelGiorno KE, Zhang T, Kraus A, French R, Jaquish D, Tsui C, Erikson G, Spike BT, Shokhirev MN et al: Reprogramming pancreatic stellate cells via p53 activation: A putative target for pancreatic cancer therapy. PLoS One 2017, 12(12):e0189051.
Huang YH, Chen MH, Guo QL, Chen ZX, Chen QD, Wang XZ: Interleukin-10 induces senescence of activated hepatic stellate cells via STAT3-p53 pathway to attenuate liver fibrosis. Cell Signal 2020, 66:109445.
Kiaris H, Chatzistamou I, Trimis G, Frangou-Plemmenou M, Pafiti-Kondi A, Kalofoutis A: Evidence for nonautonomous effect of p53 tumor suppressor in carcinogenesis. Cancer Res 2005, 65(5):1627-1630.
Kang SY, Halvorsen OJ, Gravdal K, Bhattacharya N, Lee JM, Liu NW, Johnston BT, Johnston AB, Haukaas SA, Aamodt K et al: Prosaposin inhibits tumor metastasis via paracrine and endocrine stimulation of stromal p53 and Tsp-1. Proc Natl Acad Sci U S A 2009, 106(29):12115-12120.
Sadasivam S, Duan S, DeCaprio JA: The MuvB complex sequentially recruits B-Myb and FoxM1 to promote mitotic gene expression. Genes Dev 2012, 26(5):474-489.
Chin YR, Toker A: Function of Akt/PKB signaling to cell motility, invasion and the tumor stroma in cancer. Cell Signal 2009, 21(4):470-476.
Tape CJ, Ling S, Dimitriadi M, McMahon KM, Worboys JD, Leong HS, Norrie IC, Miller CJ, Poulogiannis G, Lauffenburger DA et al: Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation. Cell 2016, 165(7):1818.
Zhang X, Lv QL, Huang YT, Zhang LH, Zhou HH: Akt/FoxM1 signaling pathway-mediated upregulation of MYBL2 promotes progression of human glioma. J Exp Clin Cancer Res 2017, 36(1):105.
Ahmed F: Integrated Network Analysis Reveals FOXM1 and MYBL2 as Key Regulators of Cell Proliferation in Non-small Cell Lung Cancer. Front Oncol 2019, 9:1011.
Latres E, Amini AR, Amini AA, Griffiths J, Martin FJ, Wei Y, Lin HC, Yancopoulos GD, Glass DJ: Insulin-like growth factor-1 (IGF-1) inversely regulates atrophy-induced genes via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. J Biol Chem 2005, 280(4):2737-2744.
Werner H, Sarfstein R, LeRoith D, Bruchim I: Insulin-like Growth Factor 1 Signaling Axis Meets p53 Genome Protection Pathways. Front Oncol 2016, 6:159.
Ma YS, Lv ZW, Yu F, Chang ZY, Cong XL, Zhong XM, Lu GX, Zhu J, Fu D: MicroRNA-302a/d inhibits the self-renewal capability and cell cycle entry of liver cancer stem cells by targeting the E2F7/AKT axis. J Exp Clin Cancer Res 2018, 37(1):252.
Wang C, Li S, Xu J, Niu W, Li S: microRNA-935 is reduced in non-small cell lung cancer tissue, is linked to poor outcome, and acts on signal transduction mediator E2F7 and the AKT pathway. Br J Biomed Sci 2019, 76(1):17-23.
Zhou H, Guo R, Wang C: Long non-coding RNA NEAT1 accelerates cell progression in cervical cancer by regulating the miR-889-3p/E2F7 axis through the activation of the PI3K/AKT pathway. RSC Advances 2019, 9:34627-34635.