Epithelial-to-mesenchymal plasticity of cancer stem cells: therapeutic targets in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) remains one of the most common and lethal malignancies worldwide despite the development of various therapeutic strategies. A better understanding of the mechanisms responsible for HCC initiation and progression is essential for the development of more effective therapies. The cancer stem cell (CSC) model has provided new insights into the development and progression of HCC. CSCs are specialized tumor cells that are capable of self-renewal and have long-term repopulation potential. As they are important mediators of tumor proliferation, invasion, metastasis, therapy resistance, and cancer relapse, the selective targeting of this crucial population of cells has the potential to improve HCC patient outcomes and survival. In recent years, the role of epithelial-to-mesenchymal transition (EMT) in the advancement of HCC has gained increasing attention. This multi-step reprograming process resulting in a phenotype switch from an epithelial to a mesenchymal cellular state has been closely associated with the acquisition of stem cell-like attributes in tumors. Moreover, CSC mediates tumor metastasis by maintaining plasticity to transition between epithelial or mesenchymal states. Therefore, understanding the molecular mechanisms of the reprograming switches that determine the progression through EMT and generation of CSC is essential for developing clinically relevant drug targets. This review provides an overview of the proposed roles of CSC in HCC and discusses recent results supporting the emerging role of EMT in facilitating hepatic CSC plasticity. In particular, we discuss how these important new insights may facilitate rational development of combining CSC- and EMT-targeted therapies in the future.

Prostate-specific IL-6 transgene autonomously induce prostate neoplasm through amplifying inflammation in the prostate and peri-prostatic adipose tissue

“…Elevation in IL-6 expression and loss of E-cadherin have been linked with increase cancer stem cell population in various cancer types [55–57]. In this study, we did not observe positivity for cancer stem cells with markers such as CD133, OCT4, or Nanog (data not shown), suggesting that rising or re-populating of cancer stem cells is not the major mechanism by which IL-6 induces prostate tumorigenesis in current model.…”

MicroRNA-224 Promotes Pancreatic Cancer Cell Proliferation and Migration by Targeting the TXNIP-Mediated HIF1α Pathway

“…2C&D). Since epithelial-to-mesenchymal transition has been recognized as an important regulator of cancer metastasis [17], we investigated whether miR-224 contributes to metastasis in PDAC via the regulation of epithelial-to-mesenchymal transition. We found that miR-224 overexpression promoted the migration of Panc1 cells (Fig.…”

Exosome-based liquid biopsy in the management of hepatocellular carcinoma

“…Accumulating evidence implicates cancer stem cells (CSCs) in the growth and spread of HCC [61] . CSCs have the capacity for self-renewal and ability to differentiate, and have been identified to confer resistance to chemotherapy.…”

“…The process of EMT is also a major contributor for metastasis and drug resistance [61] . More recently, exosomes have been described to mediate EMT in many cancers [63] .…”