Epithelial cell adhesion molecule overexpression regulates epithelial-mesenchymal transition, stemness and metastasis of nasopharyngeal carcinoma cells via the PTEN/AKT/mTOR pathway

Wang, Meng He; Sun, Rui; Zhou, Xiao Min; Zhang, Mei Yin; Lu, Jia; Yang, Yang; Zeng, Li; Yang, Xian; Shi, Lu; Xiao, Ruo Wen; Wang, Hui Yun; Shi, Juan

doi:10.1038/s41419-017-0013-8

Cited by 107 publications

(88 citation statements)

References 43 publications

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“…The ability of EpEX to act as a ligand for EGFR is in line with the fact that EpCAM N-terminal domain (a region that constitutes the solubilized EpEX) contains the EGF-like motif, thus possibly enabling it to interact and bind to EGFR. Moreover, EpCAM has also been reported to promote tumourigenesis in prostate [63,111] and nasopharyngeal cancer [112] by modulating the activity of PI3K/AKT/mTOR pathway. These studies, however, did not further investigate whether the modulation of the PI3K/AKT/mTOR pathway was achieved via the soluble EpEX or cytoplasmic EpICD.…”

Section: Epcam Downstream Targets In Cancermentioning

confidence: 99%

Revisiting the Roles of Pro-Metastatic EpCAM in Cancer

et al. 2020

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Epithelial cell adhesion molecule (EpCAM) is a cell surface protein that was discovered as a tumour marker of epithelial origins nearly four decades ago. EpCAM is expressed at basal levels in the basolateral membrane of normal epithelial cells. However, EpCAM expression is upregulated in solid epithelial cancers and stem cells. EpCAM can also be found in disseminated tumour cells and circulating tumour cells. Various OMICs studies have demonstrated that EpCAM plays roles in several key biological processes such as cell adhesion, migration, proliferation and differentiation. Additionally, EpCAM can be detected in the bodily fluid of cancer patients suggesting that EpCAM is a pathophysiologically relevant anti-tumour target as well as being utilized as a diagnostic/prognostic agent for a variety of cancers. This review will focus on the structure-features of EpCAM protein and discuss recent evidence on the pathological and physiological roles of EpCAM in modulating cell adhesion and signalling pathways in cancers as well as deliberating the clinical implication of EpCAM as a therapeutic target.

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Section: Epcam Downstream Targets In Cancermentioning

confidence: 99%

Revisiting the Roles of Pro-Metastatic EpCAM in Cancer

et al. 2020

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“…A study by Maetzel et al showed that EpCAM intracellular domains form a complex with β-catenin and LEF-1 which activates the transcriptions of genes such as c-Myc and cyclins A and E. Its overexpression increased the phosphorylation of AKT, mTOR, p70S6K and 4EBP1 as well as decreased PTEN expression. EpCAM regulates EMT and metastasis in vivo [127] [128]. The study of Fong et al revealed that ESA was overexpressed in PC and that it was related to shorter survival of patients with advanced PC.…”

Section: Esamentioning

confidence: 99%

Markers of pancreatic cancer stem cells and their clinical and therapeutic implications

et al. 2019

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Pancreatic cancer (PC) is the fourth most common cause of death among all cancers. Poor prognosis of PC may be caused by a prevalence of cancer stem cells (CSCs). CSCs are a population of cancer cells showing stem cell-like characteristics. CSCs have the ability to self-renew and may initiate tumorigenesis. PC CSCs express markers such as CD133, CD24, CD44, DCLK1, CXCR4, ESA, Oct4 and ABCB1. There is a wide complexity of interaction and relationships between CSC markers in PC. These markers are negative prognostic factors and are connected with tumor recurrence and clinical progression. Additionally, PC CSCs are resistant to treatment with gemcitabine. Thus, most current therapies for PC are ineffective. Numerous studies have shown, that targeting of these proteins may increase both disease-free and overall survival in PC.

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“…The association of EMT and HCC has also been reported in several clinical studies. A study of 123 HCC patient samples reported that the majority of clinically aggressive HCC samples had decreased E-cadherin expression, a marker of EMT status [91] . In addition, the study also reported that EMT transcription factors Snail and Twist were associated with poor prognosis in HCC with increased invasive and migratory potential [91] .…”

Section: Role Of Emt In Immune Checkpoint Blockade Therapymentioning

confidence: 99%

Immune checkpoint blockade therapies for HCC: current status and future implications

Shrestha¹,

Bridle²,

Crawford³

et al. 2019

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Hepatocellular carcinoma (HCC) is the most lethal and common type of liver cancer with limited treatment options at the advanced stage. The use of immune checkpoint inhibitor (ICI) based immunotherapy is exponentially increasing in the treatment of patients with advanced solid tumors. The expression of immune checkpoints on tumor cells leading to lower activity of T-cells is one of the major mechanisms of immune escape. Checkpoint blockade immunotherapies with antibodies against PD-1, PD-L1 or CTLA-4 are being investigated in clinical trials in HCC patients. ICIs have improved survival in patients with inoperable advanced stage HCC where other curative treatments are not applicable. However, the response rates remain low with only a small subset of patients responding to this therapy. There is an unmet need to identify predictive markers to select those HCC patients who would benefit from ICI therapies. Importantly, epithelial-to-mesenchymal transition (EMT), a major process driving HCC invasion and metastasis by regulating the phenotypic cellular switching from epithelial to mesenchymal state, has been implicated as a resistance mechanism associated with ICI therapies. The role of EMT as a regulator of immune checkpoint molecule in HCC is just emerging. However, the consequence of EMT as a resistance mechanism in HCC patients undergoing ICI treatments remains unexplored. In this review, we summarize the recent clinical studies with ICIs in HCC and highlight the trials underway featuring novel monotherapies and combinatorial approaches based on immune and non-immune therapies. We will discuss the ongoing efforts to discover new immune checkpoint molecules in HCC as potential drug targets. We also highlight the role of EMT in facilitating therapy resistance in HCC treated with ICIs and discuss potential strategies to circumvent resistance in ICI treated HCC patients.

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Epithelial cell adhesion molecule overexpression regulates epithelial-mesenchymal transition, stemness and metastasis of nasopharyngeal carcinoma cells via the PTEN/AKT/mTOR pathway

Cited by 107 publications

References 43 publications

Revisiting the Roles of Pro-Metastatic EpCAM in Cancer

Revisiting the Roles of Pro-Metastatic EpCAM in Cancer

Markers of pancreatic cancer stem cells and their clinical and therapeutic implications

Immune checkpoint blockade therapies for HCC: current status and future implications

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