Dataset Information

HYD-PEP06 suppresses hepatocellular carcinoma metastasis, epithelial-mesenchymal transition and cancer stem cell-like properties by inhibiting PI3K/AKT and WNT/β-catenin signaling activation.

ABSTRACT: HYD-PEP06, an endostatin-modified polypeptide, has been shown to produce effective anti-colorectal carcinoma effects through inhibiting epithelial-mesenchymal transition (EMT). However, whether HYD-PEP06 has similar suppressive effect on hepatocellular carcinoma (HCC) remained unknown. In this study, HYD-PEP06 inhibited metastasis and EMT but not proliferation in vitro. Cignal finder pathway reporter array and Western blot analysis revealed that HYD-PEP06 suppressed HCCLM3 cell metastasis and EMT by inhibiting the PI3K/AKT pathway. Moreover, HYD-PEP06 exerted anti-metastasis effects in HepG2 cancer stem-like cells (CSCs) via suppressing the WNT/β-catenin signaling pathway. Finally, in HCCLM3 tumor-bearing BALB/c nu/nu nude mice, HYD-PEP06 substantially suppressed tumor growth, lung metastasis and HCC progress. Our results suggest that HYD-PEP06 inhibits the metastasis and EMT of HCC and CSCs as well, and thus has the potential as an agent for HCC treatment.

SUBMITTER: Tian W

PROVIDER: S-EPMC8245914 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

HYD-PEP06 suppresses hepatocellular carcinoma metastasis, epithelial-mesenchymal transition and cancer stem cell-like properties by inhibiting PI3K/AKT and WNT/<i>β</i>-catenin signaling activation.

Tian Wei W Li Jiatong J Wang Zhuo Z Zhang Tong T Han Ying Y Liu Yanyan Y Chu Wenfeng W Liu Yu Y Yang Baofeng B

Acta pharmaceutica Sinica. B 20210402 6

HYD-PEP06, an endostatin-modified polypeptide, has been shown to produce effective anti-colorectal carcinoma effects through inhibiting epithelial-mesenchymal transition (EMT). However, whether HYD-PEP06 has similar suppressive effect on hepatocellular carcinoma (HCC) remained unknown. In this study, HYD-PEP06 inhibited metastasis and EMT but not proliferation <i>in vitro</i>. Cignal finder pathway reporter array and Western blot analysis revealed that HYD-PEP06 suppressed HCCLM3 cell metastasis ...[more]

PMID: 34221870

Similar Datasets

Project description:Gastric cancer is the second leading cause of cancer-related mortality and the fourth most common cancer globally. High intratumor heterogeneity of advanced gastric cancer poses great challenges to targeted therapy due to simultaneous activation of many redundant cancer-driving pathways. A central common signaling mechanism in cancer is proline-directed phosphorylation, which is further regulated by the unique proline isomerase Pin1. Pin1 inhibition exerts anticancer activity by blocking multiple cancer-driving pathways in some cancers, but its role in gastric cancer is not fully understood. Here we detected Pin1 protein expression in 1065 gastric cancer patients and paired normal tissues using immunohistochemistry and Western blot, and then examined the effects of Pin1 overexpression, and genetic and chemical Pin1 inhibition using Pin1 short hairpin RNA or small molecule inhibitor all-trans retinoic acid (ATRA) on tumorigenesis of human gastric cancer in vitro and in vivo, followed by biochemical analyses to elucidate Pin1 regulated oncogenic pathways. We found that Pin1 was significantly overexpressed in primary and metastasized tumors, with Pin1 overexpression being correlated with advanced stage and poor prognosis. Furthermore, whereas Pin1 overexpression promoted the transformed phenotype in immortalized and nontransformed human gastric cells, either genetic or chemical Pin1 inhibition in multiple human gastric cancer cells potently suppressed cell growth, G1/S transition and colony formation in vitro, as well as tumor growth in xenograft tumor models in vivo, which were further supported by downregulation of multiple key oncoproteins in PI3K/AKT and Wnt/β-catenin signaling pathways. These results not only provide the first evidence for a critical role of Pin1 in the tumorigenesis of gastric cancer but also suggest that targeting Pin1 using ATRA or other inhibitors offers an effective new therapeutic approach for treating advanced gastric cancer.

Dataset Information

HYD-PEP06 suppresses hepatocellular carcinoma metastasis, epithelial-mesenchymal transition and cancer stem cell-like properties by inhibiting PI3K/AKT and WNT/β-catenin signaling activation.

Publications

HYD-PEP06 suppresses hepatocellular carcinoma metastasis, epithelial-mesenchymal transition and cancer stem cell-like properties by inhibiting PI3K/AKT and WNT/<i>β</i>-catenin signaling activation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets