PMID- 35117720 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220501 IS - 2219-6803 (Electronic) IS - 2218-676X (Print) IS - 2218-676X (Linking) VI - 9 IP - 5 DP - 2020 May TI - Knockout of LATS1 induces neoplastic phenotype in hepatic oval cells. PG - 3564-3572 LID - 10.21037/tcr-19-2847 [doi] AB - BACKGROUND: Primary liver cancer (PLC) is the second leading cause of cancer-related death worldwide. It has been reported that PLC can be originated from malignant transformed adult hepatic progenitor cells. Mammalian large tumor suppressor kinase 1 (LATS1) is one of the core components of the Hippo pathway and it has been implicated in regulating invasion and metastasis of different cancer cell. However, the underlying connections between hepatic progenitor cells and LATS1 in the pathogenesis of PLC are still elusive. METHODS: LATS1 gene knockout (LATS1-KO) hepatic oval cells (HOCs) were constructed by the CRISPR/Cas9 system. Cell viability was evaluated by the CCK-8 assay. Cell migration was measured by scrape assay. Cell invasion was examined by Transwell assay. Cell apoptosis was evaluated by flow cytometry. The expression of LATS1 and Yes-associated protein (YAP) in HOCs was determined by Q-PCR and Western blot analysis. RESULTS: Here, we found that knockout of LATS1 significantly induced the migration and invasion of WB-F344 cells. Knockdown of YAP suppressed the neoplastic phenotype of LATS1-KO WB-F344 cells. Furthermore, overexpression of YAP promoted the migration and invasion of LATS1-KO WB-F344 cells. CONCLUSIONS: In summary, the current study demonstrated that LATS1 is required for inhibiting the neoplastic phenotype of normal hepatic progenitor cell via downregulating YAP. CI - 2020 Translational Cancer Research. All rights reserved. FAU - Sun, Qigang AU - Sun Q AD - Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital/Affiliated Hainan Hospital of Hainan Medical College, Haikou 570311, China. FAU - Wu, Changxiong AU - Wu C AD - Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital/Affiliated Hainan Hospital of Hainan Medical College, Haikou 570311, China. FAU - Fu, Cexiong AU - Fu C AD - Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital/Affiliated Hainan Hospital of Hainan Medical College, Haikou 570311, China. FAU - Chen, Pingping AU - Chen P AD - Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital/Affiliated Hainan Hospital of Hainan Medical College, Haikou 570311, China. FAU - Chen, Cheng AU - Chen C AD - Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital/Affiliated Hainan Hospital of Hainan Medical College, Haikou 570311, China. FAU - Liu, Jun AU - Liu J AD - Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital/Affiliated Hainan Hospital of Hainan Medical College, Haikou 570311, China. FAU - Li, Shibing AU - Li S AD - Department of Pediatric surgery, Hainan General Hospital/Affiliated Hainan Hospital of Hainan Medical College, Haikou 570311, China. FAU - Zheng, Jinfang AU - Zheng J AD - Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital/Affiliated Hainan Hospital of Hainan Medical College, Haikou 570311, China. LA - eng PT - Journal Article PL - China TA - Transl Cancer Res JT - Translational cancer research JID - 101585958 PMC - PMC8798110 OTO - NOTNLM OT - Primary liver cancer (PLC) OT - Yes-associated protein (YAP) OT - hepatic oval cells (HOCs) OT - large tumor suppressor kinase 1 (LATS1) OT - migration and invasion COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-19-2847). The authors have no conflicts of interest to declare. EDAT- 2020/05/01 00:00 MHDA- 2020/05/01 00:01 PMCR- 2020/05/01 CRDT- 2022/02/04 05:51 PHST- 2019/12/17 00:00 [received] PHST- 2020/04/10 00:00 [accepted] PHST- 2022/02/04 05:51 [entrez] PHST- 2020/05/01 00:00 [pubmed] PHST- 2020/05/01 00:01 [medline] PHST- 2020/05/01 00:00 [pmc-release] AID - tcr-09-05-3564 [pii] AID - 10.21037/tcr-19-2847 [doi] PST - ppublish SO - Transl Cancer Res. 2020 May;9(5):3564-3572. doi: 10.21037/tcr-19-2847.