Angiopoietin‐like protein 1 antagonizes MET receptor... : Hepatology (original) (raw)

Hepatobiliary Malignancies

Angiopoietin‐like protein 1 antagonizes MET receptor activity to repress sorafenib resistance and cancer stemness in hepatocellular carcinoma

Chen, Hsin‐An1,2,3,†; Kuo, Tsang‐Chih4,†; Tseng, Chi‐Feng5,6,†; Ma, Jui‐Ti5; Yang, Shu‐Ting5; Yen, Chia‐Jui7; Yang, Ching‐Yao8; Sung, Shian‐Ying9; Su, Jen‐Liang*,5,10,11,12

1Graduate Institute of Clinical Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan

2Division of General Surgery, Department of Surgery, Shuang Ho HospitalTaipei Medical UniversityNew Taipei CityTaiwan

3Division of General Surgery, Department of Surgery, School of Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan

4Institute of Biochemical Sciences, College of Life ScienceNational Taiwan UniversityTaipeiTaiwan

5National Institute of Cancer ResearchNational Health Research InstitutesZhunanTaiwan

6Graduate Program of Biotechnology in Medicine College of Life ScienceNational Tsing Hua UniversityHsinchuTaiwan

7Division of Hematology‐Oncology, Department of Internal MedicineNational Cheng Kung University HospitalTainanTaiwan

8Department of SurgeryNational Taiwan University HospitalTaipeiTaiwan

9Program for Translational Medicine, College of Medical Science and TechnologyTaipei Medical UniversityTaipeiTaiwan

10Graduate Institute of Biomedical SciencesChina Medical UniversityTaichungTaiwan

11Center for Molecular MedicineChina Medical University HospitalTaichungTaiwan

12Department of BiotechnologyAsia UniversityTaichungTaiwan

* ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO:
Jen‐Liang Su, Ph.D.
National Institute of Cancer Research
National Health Research Institutes
No. 35, Keyan Road
Zhunan, Miaoli County 35053, Taiwan
E‐mail: [email protected]
Tel: +886‐37‐246‐166

†These authors share co‐first authorship.

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Erratum

Abstract

Angiopoietin‐like protein 1 (ANGPTL1) has been shown to act as a tumor suppressor by inhibiting angiogenesis, cancer invasion, and metastasis. However, little is known about the effects of ANGPTL1 on sorafenib resistance and cancer stem cell properties in hepatocellular carcinoma (HCC) and the mechanism underlying these effects. Here, we show that ANGPTL1 expression positively correlates with sorafenib sensitivity in HCC cells and human HCC tissues. ANGPTL1 significantly decreases epithelial‐mesenchymal transition (EMT)‐driven sorafenib resistance, cancer stemness, and tumor growth of HCC cells by repressing Slug expression. ANGPTL1 directly interacts with and inactivates MET receptor, which contributes to Slug suppression through inhibition of the extracellular receptor kinase/protein kinase B (ERK/AKT)‐dependent early growth response protein 1 (Egr‐1) pathway. ANGPTL1 expression inversely correlates with Slug expression, poor sorafenib responsiveness, and poor clinical outcomes in HCC patients. Conclusion: ANGPTL1 inhibits sorafenib resistance and cancer stemness in HCC cells by repressing EMT through inhibition of the MET receptor−AKT/ERK−Egr‐1−Slug signaling cascade. ANGPTL1 may serve as a novel MET receptor inhibitor for advanced HCC therapy. (Hepatology 2016;64:1637‐1651)

Erratum

In the November 2016 issue of Hepatology, in the article titled “Angiopoietin‐like Protein 1 Antagonizes MET Receptor Activity to Repress Sorafenib Resistance and Cancer Stemness in Hepatocellular Carcinoma” (volume 64, pages 1637‐1651; doi: <10.1002/hep.28773>), by Hsin‐An Chen, Tsang‐Chih Kuo, Chi‐Feng Tseng, Jui‐Ti Ma, Shu‐Ting Yang, Chia‐Jui Yen, Ching‐Yao Yang, Shian‐Ying Sung, and Jen‐Liang Su, the representative image of flow cytometry assay of CD133 in Huh7/shANGPTL1/shLuc in Fig. 3B was incorrect. The correct image is as follows:

We apologize for this mistake.

Hepatology. 65(2):760, February 2017.