Shp2 promotes liver cancer stem cell expansion by augmenting β‐catenin signaling and predicts chemotherapeutic response of patients

Xiang, Di; Cheng, Zhuo; Liu, Hui; Wang, Xue; Han, Tao; Sun, Wen; Li, Xiaofeng; Yang, Wen; Chen, Cheng; Xia, Mingyang; Liu, Na; Yin, Shengyong; Jin, Guang‐Zhi; Lee, Terence; Dong, Liwei; Hu, He-Ping; Wang, Hongyang; Ding, Jin

doi:10.1002/hep.28919

Cited by 130 publications

(81 citation statements)

References 52 publications

(122 reference statements)

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“…All sections displaying immunohistochemical staining were observed and measured under an Olympus microscope (IX-70 OLYMPUS, Japan). The integrated optical density (IOD) was measured and calculated as IOD/total area of each image [30,31]. High Nogo-B expression is defined as sections in which the signal for positive staining was higher than the median value.…”

Section: Immunohistochemistry and Microarray Analysismentioning

confidence: 99%

WITHDRAWN: Endothelial Nogo-B suppresses cancer cell proliferation via a paracrine TGF-β/Smad signaling

Li¹,

Cheng²,

Huang³

et al. 2018

Oncotarget

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Section: Immunohistochemistry and Microarray Analysismentioning

confidence: 99%

WITHDRAWN: Endothelial Nogo-B suppresses cancer cell proliferation via a paracrine TGF-β/Smad signaling

Li¹,

Cheng²,

Huang³

et al. 2018

Oncotarget

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“…In other studies, SHP2 has also been shown to play different roles in the occurrence and development of liver cancer. SHP2‐knockout mice were found to develop liver cancer; however, SHP2 was also found to be highly expressed in clinical liver cancer samples and thus shown to be involved in the progression of liver cancer . Therefore, the role of SHP2 in different organs must be elucidated in further studies.…”

Section: Discussionmentioning

confidence: 99%

The gain‐of‐function mutation E76K in SHP2 promotes CAC tumorigenesis and induces EMT via the Wnt/β‐catenin signaling pathway

Zhang

Zhao

et al. 2018

Molecular Carcinogenesis

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SHP2 is encoded by the protein tyrosine phosphatase 11 (Ptpn11) gene. Several gain-of-function (GOF) mutations in Ptpn11 have been identified in human hematopoietic malignancies and solid tumors. In addition, the mutation rate for SHP2 is the highest for colorectal cancer (CRC) among solid tumors. The E76K GOF mutation is the most common and active SHP2 mutation; however, the pathogenic effects and function of this mutation in CRC tumor progression have not been well characterized. The Wnt/β-catenin (CTNNB1) signaling pathway is crucial for CRC, and excessive activation of this pathway has been observed in several tumors. We used Ptpn11 conditional knock-in mice to study this GOF mutation in colitis-associated CRC (CAC) and used the CRC cell lines HT29 and HCT116 to determine the relationship between SHP2 and Wnt/β-catenin signaling. Ptpn11 conditional knock-in mice exhibited aggravated inflammation and increased CAC tumorigenesis. In vitro, SHP2 and SHP2 promoted malignant biological behaviors of CRC cells and induced epithelial-mesenchymal transition (EMT) via the Wnt/β-catenin signaling pathway. Together, our results showed that SHP2 acts as an oncogene that promotes the tumorigenesis and metastasis of CRC.

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“…3 Moreover, most HCC patients do not benefit from conventional therapy, including transcatheter arterial chemoembolization (TACE) or radiotherapy. 4,5 Sorafenib is currently the only FDA-approved targeted drug for advanced HCC, but this treatment is not very effective. 6 Therefore, it is urgent to uncover the underlying mechanism of HCC and to explore new therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

“…Various numbers of hepatoma cells(2,4,8,16,32, and 64 cells per well) were seeded into 96-well ultra-low attachment and cultured in DMEM/F12 (Gibco) supplemented with 1% FBS, 20 ng/mL bFGF and 20 ng/mL EGF for 7 days. CSC proportions were analyzed using Poisson distribution statistics and the L-Calc Version 1.1 software program (Stem Cell Technologies, Inc, Vancouver, Canada).2.8 | Real-time polymerase chain reactionTotal RNA was extracted from cells using TRIzol reagent (Invitrogen, Carlsbad, CA) according to the manufacturer's instructions.…”

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confidence: 99%

Exosome‐transmitted p120‐catenin suppresses hepatocellular carcinoma progression via STAT3 pathways

Cheng

Lei

Yang

et al. 2019

Molecular Carcinogenesis

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Hepatocellular carcinoma (HCC) is a fatal disease with increasing morbidity and poor prognosis due to surgical recurrence and metastasis. Moreover, the molecular mechanism of HCC progression remains unclear. Although the role of p120-catenin (p120ctn) in liver cancer is well studied, the effects of secreted p120ctn transported by exosomes are less understood. Here, we show that p120ctn in exosomes secreted from liver cancer cells suppresses HCC cell proliferation and metastasis and expansion of liver cancer stem cells (CSCs). Mechanically, exosome p120ctn inhibits HCC cell progression via the STAT3 pathway, and the STAT3 inhibitor S3I-201 abolishes the observed effects on growth, metastasis, and self-renewal ability between exosome p120ctn-treated HCC cells and control cells. Taken together, we propose that p120ctn-containing exosomes derived from cancer cells inhibit the progression of liver cancer and may offer a new therapeutic strategy. K E Y W O R D S exosome, hepatocellular carcinoma, p120-catenin, STAT3 Molecular Carcinogenesis. 2019;58:1389-1399.wileyonlinelibrary.com/journal/mc

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Shp2 promotes liver cancer stem cell expansion by augmenting β‐catenin signaling and predicts chemotherapeutic response of patients

Abstract: Shp2 could promote HCC cell dedifferentiation and liver CSC expansion by amplifying β-catenin signaling and may be useful in predicting patient response to chemotherapeutics. (Hepatology 2017;65:1566-1580).

Cited by 130 publications

References 52 publications

WITHDRAWN: Endothelial Nogo-B suppresses cancer cell proliferation via a paracrine TGF-β/Smad signaling

WITHDRAWN: Endothelial Nogo-B suppresses cancer cell proliferation via a paracrine TGF-β/Smad signaling

The gain‐of‐function mutation E76K in SHP2 promotes CAC tumorigenesis and induces EMT via the Wnt/β‐catenin signaling pathway

Exosome‐transmitted p120‐catenin suppresses hepatocellular carcinoma progression via STAT3 pathways

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