Association of Jagged1 expression with malignancy and prognosis in human pancreatic cancer
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ORIGINAL PAPER
Association of Jagged1 expression with malignancy and prognosis in human pancreatic cancer Jungwhoi Lee 1
&
Jungsul Lee 2 & Jae Hoon Kim 1,3
Accepted: 18 April 2020 # International Society for Cellular Oncology 2020
Abstract Purpose Pancreatic cancer is one of the most aggressive cancers. Preclinical and clinical data indicate that Notch 1 ligand jagged1 (JAG1) plays a pro-oncogenic role in several malignant cancers. As yet, however, the role of JAG1 in pancreatic cancer is poorly understood. The objective of the present study was to investigate JAG1 as a therapeutic target in human pancreatic cancer. Methods Expression levels of Notch signaling molecules were assessed using GEO datasets and Western blot analysis, respectively. Anti-tumor effects following JAG1 silencing were evaluated using in vitro and in vivo assays. Prognostic implications were assessed using GEO datasets. Results Using GEO datasets and Western blot analysis we detected significantly higher JAG1 mRNA and protein expression levels in pancreatic cancer compared to normal pancreatic tissues. JAG1 silencing significantly restrained the growth, migration and invasion of pancreatic cancer cells through the induction of apoptosis and blockade of various kinases independent of the Notch1 pathway. Combined JAG1 silencing and gemcitabine treatment showed synergistic anti-viability effects in human pancreatic cancer cells. JAG1 silencing also resulted in significant anti-cancer effects in vivo and high JAG1 expression was found to be associated with an adverse prognosis in pancreatic cancer patients. Conclusions From our data we conclude that JAG1 may be a promising therapeutic target in pancreatic cancer. Keywords Pancreatic cancer . Drug-resistance . JAG1 . Notch1 . Therapeutic target
1 Introduction Pancreatic cancer is one of the most devastating cancers. The overall 5-year survival rate is only 7% [1]. Although many researchers have developed state-of-the-art therapies to remedy pancreatic cancer, the overall survival of patients with Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13402-020-00527-3) contains supplementary material, which is available to authorized users. * Jungwhoi Lee [email protected] * Jae Hoon Kim [email protected] 1
Department of Applied Life Science, SARI, Jeju National University, 102 Jejudaehak-ro, Jeju-si, Jeju-do 63243, Republic of Korea
2
Department of Bio and Brain Engineering, KAIST, Daejeon 34141, Republic of Korea
3
Subtropical/tropical Organism Gene Bank, Jeju National University, Jeju-do 63243, Republic of Korea
pancreatic cancer has not been improved in the last few decades [2]. The poor survival of pancreatic cancer patients may be attributed to several features such as vicious migratory activity, incorrigible refractory potential to conventional therapies and difficulty to diagnose [3–5]. In addition, the molecular mechanisms underlying pancreatic cancer are still unclear and efficacious therapies to overcome this aggressive neoplasm are
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