Blockade of autophagy reduces pancreatic cancer stem cell activity and potentiates the tumoricidal effect of gemcitabine

Wang, Hao‐Chen; Yang, Ming-Chen; Hou, Ya–Chin; Tung, Hui-Ling; Chiu, Tai‐Jan; Shan, Yan–Shen

doi:10.1016/j.pan.2015.05.100

Cited by 25 publications

(33 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings suggest that PaCa CD44 + /CD24 + CSCs are responsible for gemcitabine resistance and, thus, poor prognosis. A study also demonstrated that gemcitabine-resistant human PaCa tissues, which are rich in PaCa CD133 + CSCs, are highly tumorigenic, as they are capable both of forming colonies and resisting conventional chemotherapy (44). A cell adhesion molecule called CXCR4, the receptor for CXCL12 (stromal cell-derived factor-1, SDF1) that was found only at the invasive margin of the tumor, was shown to be responsible for the difference in response to therapies, leading to metastasis in a murine model (18).…”

Section: Major Obstacles and Potential Strategies For Targeting Pancrmentioning

confidence: 99%

Pancreatic Cancer Stem Cells and Therapeutic Approaches

Ercan

Karlıtepe

Özpolat³

2017

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest human cancers, with 1-5% 5-year survival rates (~6-month median survival duration) despite therapy; thus, PDAC represents an unmet therapeutic challenge. PDAC is the major histological subtype, comprising 90% of all pancreatic cancers. It is a highly complex and aggressive malignancy, presenting with early local invasion and metastasis, and is resistant to most therapies, all of which are believed to contribute to its extremely poor prognosis. PDAC is characterized by molecular alterations, including mutations of K-RAS (~90% of cases), TP53, transforming growth factor-β, Hedgehog, WNT and NOTCH signaling pathways. Given that cancer stem cells have a crucial role not only in tumor initiation and progression, but also in drug resistance and relapse or recurrence of various cancer types, they may be excellent targets for effective novel therapeutic approaches. Here, we reviewed recent therapeutic strategies targeting pancreatic cancer stem cells using chemotherapeutics and targeted drugs, non-coding RNAs (i.e., siRNA and miRNAs), immunotherapy, and natural compounds.

show abstract

Section: Major Obstacles and Potential Strategies For Targeting Pancrmentioning

confidence: 99%

Pancreatic Cancer Stem Cells and Therapeutic Approaches

Ercan

Karlıtepe

Özpolat³

2017

View full text Add to dashboard Cite

show abstract

“…These authors proposed that autophagy is essential for the function of hematopoietic stem cells, and autophagy inhibition might lead to the loss of stemness and malignancy . Yang et al reported a positive correlation between LC3, an important autophagy molecule, and the cancer stemness markers ALDH, CD44, and CD133 in pancreatic cancer tissues via microarrays analysis, and their high expression is associated with poor prognosis of patients . Xue et al discovered in hepatic progenitor cells (HPCs) that the loss of autophagy reduced colony formation and sphere formation abilities.…”

Section: Discussionmentioning

confidence: 99%

BRCA1 affects the resistance and stemness of SKOV3‐derived ovarian cancer stem cells by regulating autophagy

You

Jiang

et al. 2019

Cancer Medicine

View full text Add to dashboard Cite

Breast cancer 1 (BRCA1) and autophagy both play a significant role in drug resistance. However, little is known about the dynamic cross talk between BRCA1 and autophagy in the regulation of drug sensitivity. Here, we investigated the drug resistance‐associated regulation of BRCA1 in epithelial ovarian cancer stem cells (EOCSCs). The results indicated that BRCA1 could regulate drug resistance in EOCSCs. Autophagy played a significant role in the stemness maintenance and was a key mechanism underlying the survival against chemotherapy in EOCSCs. Further investigation found that BRCA1 could regulate drug resistance of EOCSCs through autophagy. Meanwhile, changes in the level of autophagy provided feedback regarding the expression of BRCA1. Inhibition of autophagy activity could effectively reduce the resistance of EOCSCs caused by BRCA1. In addition, BRCA1 was able to regulate cellular apoptosis and cell cycle progression under the action of cisplatin through autophagy, indirectly affecting the drug sensitivity of EOCSCs. The present results highlight a novel relationship between BRCA1 and autophagy, which may provide insight into the etiology of BRCA1‐associated ovarian cancer, and improve our understanding of resistance mechanisms in ovarian cancer.

show abstract

“…Alterations in the relevant signaling pathways are observed in many human malignancies . There is solid evidence to support that autophagy maintains the survival of cancer cells by conferring stress tolerance and limiting damage . Furthermore, it was shown that autophagy is related to UC grade, and contributes to the maintenance of cellular bioenergetics and cancer cell survival …”

Section: Autophagymentioning

confidence: 99%

“…Interestingly, the induction of autophagy, which is mediated by osteopontin/nuclear factor‐κB signaling, is required for the maintenance of pancreatic CSC activity, which indicates that the combination of gemcitabine with pharmacological autophagy inhibitors could be a promising therapeutic strategy for pancreatic cancer . The inhibition of autophagy might be a useful way to increase the effects of treatment on CSCs.…”

Section: Autophagymentioning

confidence: 99%

Cancer stem cells and epithelial–mesenchymal transition in urothelial carcinoma: Possible pathways and potential therapeutic approaches

Fang

Kitamura

2017

Int J of Urology

View full text Add to dashboard Cite

Abbreviations & Acronyms ALDH = aldehyde dehydrogenase AR = androgen receptor BCG = bacillus Calmette-Gu erin CD = cluster of differentiation COX-2 = cyclooxygenase-2 CSC = cancer stem cell CT = cancer testis EMT = epithelial-mesenchymal transition JAK2 = Janus kinase 2 MAGE = melanoma-associated antigen malat1 = metastasis-associated lung adenocarcinoma transcript 1 MAPK = mitogen-activated protein kinase MC-A = myrtucommulone-A MIBC = muscle-invasive bladder cancer miRNA = micro-ribonucleic acid OCT = octamer-binding transcription factor PD-1 = programmed cell death protein 1 PGE2 = prostaglandin E2 PI3K = phosphatidylinositol-3-kinase PRC = polycomb repressive complex Shh = sonic hedgehog SOX = sex-determining region of the Y chromosome-related high mobility group box SP = side population STAT3 = signal transducer and activator of transcription 3 TGF = transforming growth factor UCSC = urothelial cancer stem cell UTUC = upper tract urothelial carcinoma Abstract: There is growing evidence of the presence of cancer stem cells in urothelial carcinoma. Cancer stem cells have the ability to self-renew and to differentiate into all cell types of the original heterogeneous tumor. A panel of diverse cancer stem cell markers might be suitable for simulation studies of urothelial cancer stem cells and for the development of optimized treatment protocols. The present review focuses on the advances in recognizing the markers of urothelial cancer stem cells and possible therapeutic targets. The commonly reported markers and pathways that were evaluated include CD44, CD133, ALDH1, SOX2 & SOX4, BMI1, EZH1, PD-L1, MAGE-A3, COX2/PGE2/ STAT3, AR, and autophagy. Studies on the epithelial-mesenchymal transition-related pathways (Shh, Wnt/b-catenin, Notch, PI3K/Akt, TGF-b, miRNA) are also reviewed. Most of these markers were recognized through the expression patterns of cancer stem cell-rich side populations. Their regulative role in the development and differentiation of urothelial cancer stem cells was confirmed in vitro by functional analyses (e.g. cell migration, colony formation, sphere formation), and in vivo in xenograft experiments. Although a small number of these pathways are targeted by currently available drugs or drugs that are the currently being tested in clinical trials, a clear treatment approach has not been developed for most pathways. A greater understanding of the mechanisms that control the proliferation and differentiation of cancer stem cells is expected to lead to improvements in targeted therapy.

show abstract

Blockade of autophagy reduces pancreatic cancer stem cell activity and potentiates the tumoricidal effect of gemcitabine

Cited by 25 publications

References 39 publications

Pancreatic Cancer Stem Cells and Therapeutic Approaches

Pancreatic Cancer Stem Cells and Therapeutic Approaches

BRCA1 affects the resistance and stemness of SKOV3‐derived ovarian cancer stem cells by regulating autophagy

Cancer stem cells and epithelial–mesenchymal transition in urothelial carcinoma: Possible pathways and potential therapeutic approaches

Contact Info

Product

Resources

About