Inhibition of hedgehog signaling depresses self-renewal of pancreatic cancer stem cells and reverses chemoresistance

Huang, Fengting; Zhuansun, Yongxun; Zhuang, Yanyan; Wei, Shuli; Tang, Jian; Chen, Wenbo; Zhang, Shineng

doi:10.3892/ijo.2012.1597

Cited by 86 publications

(61 citation statements)

References 33 publications

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“…These molecules modulate growth, proliferative, migration, and apoptotic pathways, often resulting in metastasis and advanced stage disease (33)(34)(35)(36)(37)(38)(39)(40). Next, we evaluated expression of a panel of cytokines associated with disease progression using pancreas tumor tissues from the same cohort in the previous section by qPCR.…”

Section: Resultsmentioning

confidence: 99%

Inactivation of the Transcription Factor GLI1 Accelerates Pancreatic Cancer Progression

Mills

Zhang²,

Marler

et al. 2014

Journal of Biological Chemistry

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Background: GLI1 is required for pancreatic tumor initiation; however, its role at later stages of carcinogenesis remains elusive. Results: Genetic inactivation of GLI1 accelerates pancreatic cancer progression. Conclusion: GLI1 can act as both a promoter and suppressor of pancreatic carcinogenesis depending on the tumor stage. Significance: This knowledge increases our understanding of pancreatic carcinogenesis and may help the design of therapies targeting GLI1-related pathways.

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Section: Resultsmentioning

confidence: 99%

Inactivation of the Transcription Factor GLI1 Accelerates Pancreatic Cancer Progression

Mills

Zhang²,

Marler

et al. 2014

Journal of Biological Chemistry

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“…Hedgehog (Hh) signaling, that is implicated in the initiation and progression of PDAC, also contributes to desmoplasia [100]. A combination therapy comprising GDC-0449 (inhibitor of Hh pathway) and the miR-let7b mimic, effectively inhibited tumor growth when injected to athymic nude mice bearing ectopic tumors, compared with micelles carrying GDC-0449 or miR-let7b alone.…”

Section: • Combination Of Anticancer Agents and Mirna Modulators Effectmentioning

confidence: 99%

Developments in Mirna Gene Signaling Pathways in Pancreatic Cancer

2016

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Pancreatic cancer is a devastating malignancy that ranks as the fourth leading cause of cancerrelated deaths worldwide. Dismal prognosis is mainly attributable to limited knowledge of the molecular pathogenesis of the disease. miRNAs have been found to be deregulated in pancreatic cancer, affecting several steps of initiation and aggressiveness of the disease by regulating important signaling pathways, such as the KRAS and Notch pathways. Moreover, the effect of miRNAs on regulating cell cycle events and expression of transcription factors has gained a lot of attention. Recent studies have highlighted the application of miRNAs as biomarkers and therapeutic tools. The current review focuses on latest advances with respect to the roles of miRNAs in pancreatic ductal adenocarcinoma associated signaling pathways and miRNA-based therapeutics. KEYWORDS• antisense oligonucleotides • miRNAs • pancreatic cancer Pancreatic cancer overview Pancreatic ductal adenocarcinoma (PDAC) is the predominant form of pancreatic neoplasms and accounts for greater than 85% of the clinical cases [1]. The disease develops via acinar-ductal metaplasia and neoplastic precursor lesions [2]. In the USA alone, 48,960 new cases of pancreatic cancer were expected to occur in 2015, with an estimated 40,560 deaths, about the same number in women (19,850) as in men (20,710). Over 96% are cancers arising from exocrine pancreas. Endocrine carcinomas are often diagnosed at a younger age and exhibit a better prognosis. From 2007 to 2011, mortality rates increased slightly by 0.3% per year. For all stages combined, the 1-and 5-year relative survival rates are 28 and 7%, respectively. For the small percentage of people diagnosed with local disease (9%), the 5-year survival is 26%, while more than half of patients (53%) are diagnosed at a late stage for which 1-and 5-year survival rates reach 15 and 2%, respectively [3]. These numbers are a staggering example of the poor prognosis associated with PDAC.While new therapeutic options are emerging for nonhematologic malignancies, molecular-targeted therapies for pancreatic cancer have failed to make any positive impact on patient survival. In 1993, the Nobel Prize-winning discovery of small interference RNAs (siRNAs) led to an outburst of knowledge on RNA interference and gene regulation [4]. Since then, thousands of research studies have described the functional role of small noncoding RNAs, named miRNAs, in a vast panel of human pathologies. In 2002, a small genomic region in chromosome 13q14 comprising miR-15a and miR-16-1 genes was found to be commonly deleted in chronic lymphocytic leukemia, For reprint orders, please contact: reprints@futuremedicine.com

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“…Recently, mounting evidence supports hedgehog signaling activation in pancreatic CSCs. Hedgehog pathway plays a significant role by regulating pluripotency maintaining factors like Oct4, Nanog, c-Myc, and Sox2 to the maintenance of stemness [61][62][63][64][65][66] . Apart from hedgehog, increasing evidence suggests that Notch signaling activation was associated with molecular characteristics of CSCs in PC cases [67,68] .…”

Section: Signaling Pathways Altered By Cscsmentioning

confidence: 99%

New insights into pancreatic cancer stem cells

Rao¹,

Mohammed²

2015

WJSC

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Pancreatic cancer (PC) has been one of the deadliest of all cancers, with almost uniform lethality despite aggressive treatment. Recently, there have been important advances in the molecular, pathological and biological understanding of pancreatic cancer. Even after the emergence of recent new targeted agents and the use of multiple therapeutic combinations, no treatment option is viable in patients with advanced cancer. Developing novel strategies to target progression of PC is of intense interest. A small population of pancreatic cancer stem cells (CSCs) has been found to be resistant to chemotherapy and radiation therapy. CSCs are believed to be responsible for tumor initiation, progression and metastasis. The CSC research has recently achieved much progress in a variety of solid tumors, including pancreatic cancer to some extent. This leads to focus on understanding the role of pancreatic CSCs. The focus on CSCs may offer new targets for prevention and treatment of this deadly cancer. We review the most salient developments in important areas of pancreatic CSCs. Here, we provide a review of current updates and new insights on the role of CSCs in pancreatic tumor progression with special emphasis on DclK1 and Lgr5, signaling pathways altered by CSCs, and the role of CSCs in prevention and treatment of PC.

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Inhibition of hedgehog signaling depresses self-renewal of pancreatic cancer stem cells and reverses chemoresistance

Cited by 86 publications

References 33 publications

Inactivation of the Transcription Factor GLI1 Accelerates Pancreatic Cancer Progression

Inactivation of the Transcription Factor GLI1 Accelerates Pancreatic Cancer Progression

Developments in Mirna Gene Signaling Pathways in Pancreatic Cancer

New insights into pancreatic cancer stem cells

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