title: PS341 inhibits hepatocellular and colorectal cancer cells through the FOXO3/CTNNB1 signaling pathway.
abstract: Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are among the most common cancers across the world. Particularly, a large number of patients with CRC also have liver metastasis. Currently, there are just a few targeted drugs against these two kinds of tumors which can only benefit a very small population of patients. Therefore, the need of more effective therapeutic drugs or strategies for these two types of cancers is urgent. PS341 (Bortezomib) is the first proteasome inhibitor drug which has been approved in clinical treatment for multiple myeloma. Here we demonstrated that PS341 negatively regulated HCC and CRC both in vitro and in vivo, including the inhibition of cell proliferation, epithelial-mesenchymal transition (EMT), the expression of stemness-related genes, cell migration and invasiveness. Mechanically, PS341 upregulated the expression of FOXO3, which inhibited the transcriptional activation of CTNNB1. The downregualtion of CTNNB1 led to apoptosis, cell cycle arrest, and the inhibition of migration, invasion, self-renewal and tumor formation of these two cancer types. In sum, our findings shed light on the PS341 mediated targeted therapy against both HCC and CRC in the future.
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: Shengwu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Soochow University, Suzhou, 215000, China.
authors.forename: Mingao
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Soochow University, Suzhou, 215000, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Soochow University, Suzhou, 215000, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Soochow University, Suzhou, 215000, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Soochow University, Suzhou, 215000, China.
authors.forename: Kaisu
authors.initials: K
authors.lastname: Lin
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Xiumin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Min
authors.initials: M
authors.lastname: Tao
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China.|Laboratory Animal Center, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000069286:Bortezomib / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D000071316:Forkhead Box Protein O3 / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D051176:beta Catenin / Q000187:drug effects*
chemical_list: C495270:CTNNB1 protein, human; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051176:beta Catenin; D000069286:Bortezomib