The Epithelial to Mesenchymal Transition (EMT) and Cancer Stem Cells: Implication for Treatment Resistance in Pancreatic Cancer

Overview

Journal Mol Cancer

Publisher Biomed Central

Specialties Molecular Biology
Oncology

Date 2017 Mar 2

PMID 28245823

Citations 163

Authors

Pingting Zhou

Bo Li

Furao Liu

Meichao Zhang

Qian Wang

YuanHua Liu

Yuan Yao

Dong Li

Affiliations

Soon will be listed here.

Abstract

The mechanical properties of epithelial to mesenchymal transition (EMT) and a pancreatic cancer subpopulation with stem cell properties have been increasingly recognized as potent modulators of the effective of therapy. In particular, pancreatic cancer stem cells (PCSCs) are functionally important during tumor relapse and therapy resistance. In this review we have surveyed recent advances in the role of EMT and PCSCs in tumor progression, metastasis and treatment resistance, and the mechanisms of integrated with biochemical signals and the underlying pathways involved in treatment resistance of pancreatic cancer. These findings highlight the importance of confirming stem-cells markers and complex molecular signaling pathways controlling EMT and cancer stem cells in pancreatic cancer during tumor formation, progression, and response to therapy.

Citing Articles

New insights into Notch signaling as a crucial pathway of pancreatic cancer stem cell behavior by chrysin-polylactic acid-based nanocomposite.

Ragab E, El Gamal D, El-Najjar F, Elkomy H, Ragab M, Elantary M Discov Oncol. 2025; 16(1):107.

PMID: 39891818 PMC: 11787125. DOI: 10.1007/s12672-025-01846-3.

ITGAX promotes gastric cancer progression via epithelial-mesenchymal transition pathway.

Hu J, Cao J, Huang S, Chen Y Front Pharmacol. 2025; 15():1536478.

PMID: 39845786 PMC: 11750855. DOI: 10.3389/fphar.2024.1536478.

Smad2 Cooperating with TGIF2 Contributes to EMT and Cancer Stem Cells Properties in Pancreatic Cancer via Co-Targeting SOX2.

Zu F, Chen C, Geng Q, Li H, Chan B, Luo G Int J Biol Sci. 2025; 21(2):524-543.

PMID: 39781447 PMC: 11705628. DOI: 10.7150/ijbs.102381.

Composition analysis and mechanism of Guizhi Fuling capsule in anti-cisplatin-resistant ovarian cancer.

Dou L, Yan Y, Lu E, Li F, Tian D, Deng L Transl Oncol. 2024; 52():102244.

PMID: 39662450 PMC: 11683237. DOI: 10.1016/j.tranon.2024.102244.

Inhibition of EREG/ErbB/ERK by Astragaloside IV reversed taxol-resistance of non-small cell lung cancer through attenuation of stemness via TGFβ and Hedgehog signal pathway.

Xiu W, Zhang Y, Tang D, Lee S, Zeng R, Ye T Cell Oncol (Dordr). 2024; 47(6):2201-2215.

PMID: 39373858 DOI: 10.1007/s13402-024-00999-7.

References

De Craene B, Berx G . Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 2013; 13(2):97-110. DOI: 10.1038/nrc3447. View

Hay E . An overview of epithelio-mesenchymal transformation. Acta Anat (Basel). 1995; 154(1):8-20. DOI: 10.1159/000147748. View

Matsuda Y, Yoshimura H, Ueda J, Naito Z, Korc M, Ishiwata T . Nestin delineates pancreatic cancer stem cells in metastatic foci of NOD/Shi-scid IL2Rγ(null) (NOG) mice. Am J Pathol. 2014; 184(3):674-85. PMC: 3936308. DOI: 10.1016/j.ajpath.2013.11.014. View

Tiwari N, Meyer-Schaller N, Arnold P, Antoniadis H, Pachkov M, van Nimwegen E . Klf4 is a transcriptional regulator of genes critical for EMT, including Jnk1 (Mapk8). PLoS One. 2013; 8(2):e57329. PMC: 3581489. DOI: 10.1371/journal.pone.0057329. View

Nieto M . The ins and outs of the epithelial to mesenchymal transition in health and disease. Annu Rev Cell Dev Biol. 2011; 27:347-76. DOI: 10.1146/annurev-cellbio-092910-154036. View

van den Hoogen C, van der Horst G, Cheung H, Buijs J, Pelger R, van der Pluijm G . The aldehyde dehydrogenase enzyme 7A1 is functionally involved in prostate cancer bone metastasis. Clin Exp Metastasis. 2011; 28(7):615-25. PMC: 3198191. DOI: 10.1007/s10585-011-9395-7. View

Peinado H, Olmeda D, Cano A . Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?. Nat Rev Cancer. 2007; 7(6):415-28. DOI: 10.1038/nrc2131. View

Matsubara S, Ding Q, Miyazaki Y, Kuwahata T, Tsukasa K, Takao S . mTOR plays critical roles in pancreatic cancer stem cells through specific and stemness-related functions. Sci Rep. 2013; 3:3230. PMC: 3828572. DOI: 10.1038/srep03230. View

Li C, Heidt D, Dalerba P, Burant C, Zhang L, Adsay V . Identification of pancreatic cancer stem cells. Cancer Res. 2007; 67(3):1030-7. DOI: 10.1158/0008-5472.CAN-06-2030. View

10.

Birchmeier C, Gherardi E . Developmental roles of HGF/SF and its receptor, the c-Met tyrosine kinase. Trends Cell Biol. 1998; 8(10):404-10. DOI: 10.1016/s0962-8924(98)01359-2. View

11.

OConnor M, Xiang D, Shigdar S, Macdonald J, Li Y, Wang T . Cancer stem cells: A contentious hypothesis now moving forward. Cancer Lett. 2013; 344(2):180-7. DOI: 10.1016/j.canlet.2013.11.012. View

12.

Lonardo E, Hermann P, Mueller M, Huber S, Balic A, Miranda-Lorenzo I . Nodal/Activin signaling drives self-renewal and tumorigenicity of pancreatic cancer stem cells and provides a target for combined drug therapy. Cell Stem Cell. 2011; 9(5):433-46. DOI: 10.1016/j.stem.2011.10.001. View

13.

Zhang J, Ma L . MicroRNA control of epithelial-mesenchymal transition and metastasis. Cancer Metastasis Rev. 2012; 31(3-4):653-62. PMC: 3686549. DOI: 10.1007/s10555-012-9368-6. View

14.

Mizuma M, Rasheed Z, Yabuuchi S, Omura N, Campbell N, de Wilde R . The gamma secretase inhibitor MRK-003 attenuates pancreatic cancer growth in preclinical models. Mol Cancer Ther. 2012; 11(9):1999-2009. PMC: 3438318. DOI: 10.1158/1535-7163.MCT-12-0017. View

15.

Quint K, Tonigold M, Di Fazio P, Montalbano R, Lingelbach S, Ruckert F . Pancreatic cancer cells surviving gemcitabine treatment express markers of stem cell differentiation and epithelial-mesenchymal transition. Int J Oncol. 2012; 41(6):2093-102. DOI: 10.3892/ijo.2012.1648. View

16.

Singh A, Settleman J . EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene. 2010; 29(34):4741-51. PMC: 3176718. DOI: 10.1038/onc.2010.215. View

17.

Xiao L, Yuan X, Sharkis S . Activin A maintains self-renewal and regulates fibroblast growth factor, Wnt, and bone morphogenic protein pathways in human embryonic stem cells. Stem Cells. 2006; 24(6):1476-86. DOI: 10.1634/stemcells.2005-0299. View

18.

Clarke M, Dick J, Dirks P, Eaves C, Jamieson C, Jones D . Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 2006; 66(19):9339-44. DOI: 10.1158/0008-5472.CAN-06-3126. View

19.

Dong C, Wu Y, Yao J, Wang Y, Yu Y, Rychahou P . G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer. J Clin Invest. 2012; 122(4):1469-86. PMC: 3314447. DOI: 10.1172/JCI57349. View

20.

Miralles F, Lamotte L, Couton D, Joshi R . Interplay between FGF10 and Notch signalling is required for the self-renewal of pancreatic progenitors. Int J Dev Biol. 2005; 50(1):17-26. DOI: 10.1387/ijdb.052080fm. View