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Hepatic neoplasm

Targeting epithelial-mesenchymal transition pathway in hepatocellular carcinoma
Jaewhan Song
Clin Mol Hepatol 2020;26(4):484-486.
Published online October 1, 2020
DOI: https://doi.org/10.3350/cmh.2020.0220

Citations

Citations to this article as recorded by  Crossref logo
  • ABCG8‑mediated sterol efflux increases cancer cell progression via the LRP6/Wnt/β‑catenin signaling pathway in radiotherapy‑resistant MDA‑MB‑231 triple‑negative breast cancer cells
    Young Ko, Ju Won, Hana Jin, Nam Nguyen, Yaeram Won, Vedaste Nsanzimana, Seung Yun, Sang Park, Hye Kim
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    Journal of Cellular and Molecular Medicine.2024;[Epub]     CrossRef
  • MCTP1 increases the malignancy of androgen-deprived prostate cancer cells by inducing neuroendocrine differentiation and EMT
    Yen-Nien Liu, Wei-Yu Chen, Hsiu-Lien Yeh, Wei-Hao Chen, Kuo-Ching Jiang, Han-Ru Li, Phan Vu Thuy Dung, Zi-Qing Chen, Wei-Jiunn Lee, Michael Hsiao, Jiaoti Huang, Yu-Ching Wen
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  • PIM1-Induced Cytoplasmic Expression of RBMY Mediates Hepatocellular Carcinoma Metastasis
    Huey-Huey Chua, Mei-Hwei Chang, Ya-Hui Chen, Daw-Jen Tsuei, Yung-Ming Jeng, Po-Huang Lee, Yen-Hsuan Ni
    Cellular and Molecular Gastroenterology and Hepatology.2023; 15(1): 121.     CrossRef
  • Clinical Significance of Combined Epithelial–Mesenchymal Transition Markers Expression and Role of Rac1 in Hepatocellular Carcinoma
    Seung Kak Shin, Sujin Ryu, Seungyoon Nam, Seung Yeon Ha, Oh Sang Kwon, Yun Soo Kim, Se-Hee Kim, Ju Hyun Kim
    International Journal of Molecular Sciences.2023; 24(2): 1765.     CrossRef
  • PI3K/AKT Signaling Tips the Balance of Cytoskeletal Forces for Cancer Progression
    Shuo Deng, Hin Chong Leong, Arpita Datta, Vennila Gopal, Alan Prem Kumar, Celestial T. Yap
    Cancers.2022; 14(7): 1652.     CrossRef
  • Concurrent Chemoradiotherapy-Driven Cell Plasticity by miR-200 Family Implicates the Therapeutic Response of Esophageal Squamous Cell Carcinoma
    Yu-Cheng Lee, Cheng-Han Lin, Wei-Lun Chang, Wen-Der Lin, Jhih-Kai Pan, Wei-Jan Wang, Bor-Chyuan Su, Hsien-Hui Chung, Chen-Hsun Tsai, Forn-Chia Lin, Wen-Ching Wang, Pei-Jung Lu
    International Journal of Molecular Sciences.2022; 23(8): 4367.     CrossRef
  • Leukocyte cell-derived chemotaxin 2 regulates epithelial-mesenchymal transition and cancer stemness in hepatocellular carcinoma
    Tian-Huei Chu, Chou-Yuan Ko, Po-Han Tai, Yi-Chen Chang, Chao-Cheng Huang, Tung-Yang Wu, Hoi-Hung Chan, Ping-Hsuan Wu, Chien-Hui Weng, Yu-Wei Lin, Mei-Lang Kung, Cheng-Chieh Fang, Jian-Ching Wu, Zhi-Hong Wen, Yung-Kuo Lee, Tsung-Hui Hu, Ming-Hong Tai
    Journal of Biological Chemistry.2022; 298(10): 102442.     CrossRef
  • MiR-23b-3p suppresses epithelial-mesenchymal transition, migration, and invasion of hepatocellular carcinoma cells by targeting c-MET
    Na Ri Park, Jung Hoon Cha, Pil Soo Sung, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Si Hyun Bae
    Heliyon.2022; 8(10): e11135.     CrossRef
  • Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1
    Tae Suk Kim, Minjong Lee, Minji Park, Sae Yun Kim, Min Suk Shim, Chea Yeon Lee, Dae Hee Choi, Yuri Cho
    International Journal of Molecular Sciences.2021; 22(18): 10027.     CrossRef
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Original Articles

Hepatic neoplasm

Inhibition of PI3K/Akt signaling suppresses epithelial-to-mesenchymal transition in hepatocellular carcinoma through the Snail/GSK-3/beta-catenin pathway
Seulki Lee, Eun Ji Choi, Eun Ju Cho, Yun Bin Lee, Jeong-Hoon Lee, Su Jong Yu, Jung-Hwan Yoon, Yoon Jun Kim
Clin Mol Hepatol 2020;26(4):529-539.
Published online August 24, 2020
DOI: https://doi.org/10.3350/cmh.2019.0056n
Background/Aims
Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis due to the lack of effective systemic therapies. Epithelial-to-mesenchymal transition (EMT) is a pivotal event in tumor progression, during which cancer cells acquire invasive properties. In this study, we investigated the effects of phosphatidylinositol 3-kinase (PI3K) inhibitors, including LY294002 and idelalisib, on the EMT features of HCC cells in vitro.
Methods
Human HCC cell lines, including Huh-BAT and HepG2, were used in this study. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, and cell cycle distributions were evaluated using a flow cytometer by propidium iodide staining. Immunofluorescence staining, quantitative real-time polymerase chain reaction, and immunoblotting were performed to detect EMT-associated changes.
Results
PI3K inhibitors suppressed the proliferation and invasion of HCC cells and deregulated the expression of EMT markers, as indicated by increased expression of E-cadherin, an epithelial marker, and decreased expression of N-cadherin, a mesenchymal marker, and Snail, a transcription factor implicated in EMT regulation. Furthermore, LY294002 and idelalisib inhibited the phosphorylation of GSK-3β and induced the nuclear translocation of GSK-3β, which corresponded to the downregulation of Snail and β-catenin expressions in Huh-BAT and HepG2 cells.
Conclusions
The inhibition of PI3K/Akt signaling decreases Snail expression by enhancing the nuclear translocation of GSK-3β, which suppresses EMT in HCC cells, suggesting the potential clinical application of PI3K inhibitors for HCC treatment.

Citations

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Co-expression patterns of Notch1, Snail, and p53 in grade III hepatocellular carcinoma with postoperative recurrence: a preliminary study
Sun Kyung Jang, Gi Hong Choi, Junjeong Choi, Xiaoyuan Quan, Jeong Won Jang, Bo Hyun Kim, Guhung Jung, Young Min Park
Korean J Hepatol 2012;18(1):63-74.
Published online March 22, 2012
DOI: https://doi.org/10.3350/kjhep.2012.18.1.63
Background/Aims

We aimed to determine the association between the co-expression patterns of Notch1, Snail, and p53 proteins (NSP) and the postoperative prognosis of hepatocellular carcinoma (HCC).

Methods

The immunoblot data for molecular expression (147 HCC/corresponding non-HCC tissues and 15 dysplastic nodules) and the sequencing data for p53 mutations (110 HCCs) were obtained from our previous study. Data analyses were restricted to cases with HCC differentiation grade III (n=47), due to its high p53 mutation rate.

Results

Nineteen of the 47 patients (40.4%) -comprising 12 in the liver and 7 in distant organs-had relapsed at 1-2 years after surgery. There was no relationship between p53 mutation and postoperative recurrence in the grade III HCCs. Seven (87.5%) of the eight relapsed cases with Notch1, Snail, and p53 (wild) co-expression experienced recurrence only within the liver, and all tumors were smaller than 5 cm in diameter. Extrahepatic relapse occurred mostly in HCC patients with tumors larger than 5 cm in diameter, without any deviation in the NSP pattern.

Conclusions

The results of this preliminary study suggest that the co-expression of Notch1, Snail, and p53 (wild) is not inferior to the patterns with p53 mutation as an indicator of postoperative recurrence of grade III HCC.

Citations

Citations to this article as recorded by  Crossref logo
  • Hepatocellular carcinoma: Where are we in 2018?
    William C. Chapman, Kevin M. Korenblat, Kathryn J. Fowler, Nael Saad, Adeel S. Khan, Vijay Subramanian, Maria B. Majella Doyle, Leigh Anne Dageforde, Benjamin Tan, Patrick Grierson, Yiing Lin, Min Xu, Elizabeth M. Brunt
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    Min Zhang, Xin Dong, Dengcai Zhang, Xiaojie Chen, Xinyu Zhu
    Oncotarget.2017; 8(3): 4543.     CrossRef
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  • Crossref
Clinicopathologic significance of the expression of Snail in hepatocellular carcinoma
Hyun Young Woo, Ae Lyoung Min, Jong Young Choi, Si Hyun Bae, Seung Kew Yoon, Chan Kwon Jung
Korean J Hepatol 2011;17(1):12-18.
Published online March 21, 2011
DOI: https://doi.org/10.3350/kjhep.2011.17.1.12
Background/Aims

E-cadherin is involved in intercellular binding and cellular polarity formation. Snail is a key regulator of the epithelial-mesenchymal transition and is closely associated with tumor invasiveness due to its ability to suppress E-cadherin expression. We investigated the expressions of E-cadherin and Snail in hepatocellular carcinoma (HCC) tissue to determine the clinical significance of these proteins in HCC.

Methods

Immunohistochemistry was used to examine the expressions of E-cadherin and Snail in resected tissues from 59 patients diagnosed with HCC. We also evaluated the relationship between the expressions of these two molecules in HCC tissue and clinicopathologic factors in the patients.

Results

Immunohistochemistry showed that Snail was stained in 20.3% of the HCC tissues and 3.4% of noncancerous tissues. Snail was not stained in the area of E-cadherin expression. The expression of Snail in the HCC tissue was associated with poorly differentiated HCC (P=0.028). The expression of Snail without E-cadherin staining in HCC tissue was significantly associated with postoperative HCC recurrence (P=0.013).

Conclusions

The expression of Snail in HCC tissue was associated with decreased expression of E-cadherin and poorly differentiated HCC. The expression of Snail without E-cadherin staining in HCC was associated with postoperative recurrence.

Citations

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