Review
Oncology
Hewen Shi, Ying Zou, Weiwei Zhong, Zhaoying Li, Xiaoxue Wang, Yancun Yin, Defang Li, Ying Liu, Minjing Li
Summary: This review summarizes the important roles of Yap/Taz in activating the Hippo pathway in liver cancer, and discusses the crosstalks between the Hippo pathway and other cancer associated pathways and molecules.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Environmental Sciences
Duanyu Su, Zhian Lin
Summary: The antitumor effects of dichloroacetate (DCA) in hepatocellular carcinoma (HCC) have been explored, showing that DCA may attenuate HCC cell stemness by activating the Hippo pathway and promoting nucleus-cytoplasm translocation of YAP. The inhibition of Hippo pathway partially abrogated DCA-induced effects on HCC cell stemness, suggesting DCA as a potential inhibitor for HCC progression.
ENVIRONMENTAL TOXICOLOGY
(2021)
Article
Cell Biology
Joelle Tchicaya-Bouanga, Yu-Jen Hung, Jean-Marc Schwartz, Diane Ji Yun Yoon, Emilie Chotard, Clarice Marty, Guillaume Anthony Odri, Gonzague de Pinieux, Martine Cohen-Solal, Dominique Modrowski
Summary: This study reveals the involvement of calpain-6 in promoting tumor growth and metastasis in sarcoma stem cells. Calpain-6 modulates the expression of Hippo pathway genes and stabilizes YAP, as well as regulates the vesicular trafficking of beta-catenin degradation complexes. The expression of calpain-6 is associated with genes related to the G2M phase of the cell cycle and up-regulated genes controlling mitosis in sarcoma stem cells and tissues. In mouse models, YAP inhibition prevents the formation of primary tumors and metastases, but has no effect on already established tumors and can even accelerate lung metastasis associated with large bone tumors.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Yu-Chuan Yan, Guang-Xiao Meng, Chun-Cheng Yang, Ya-Fei Yang, Si-Yu Tan, Lun-Jie Yan, Zi-Niu Ding, Yun-Long Ma, Zhao-Ru Dong, Tao Li
Summary: In this study, the DAGLA/2-AG axis is found to promote HCC progression by regulating cell proliferation, invasion, and metastasis. Furthermore, DAGLA induces resistance to lenvatinib therapy during HCC treatment. Therefore, inhibiting the DAGLA/2-AG axis could be a novel therapeutic strategy to inhibit HCC progression and enhance the therapeutic effects of TKIs.
CELL DEATH & DISEASE
(2023)
Article
Gastroenterology & Hepatology
Haichuan Wang, Jingxiao Wang, Shanshan Zhang, Jiaoyuan Jia, Xianqiong Liu, Jie Zhang, Pan Wang, Xinhua Song, Li Che, Ke Liu, Silvia Ribback, Antonio Cigliano, Matthias Evert, Hong Wu, Diego F. Calvisi, Yong Zeng, Xin Chen
Summary: YAP and TAZ play overlapping and distinct roles in hepatocarcinogenesis. HCCs may exhibit unique activation of either YAP or TAZ, thus relying on either YAP or TAZ for their growth.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Cell Biology
Shugeng Zhang, Shuhang Liang, Dehai Wu, Hongrui Guo, Kun Ma, Lianxin Liu
Summary: The study reveals a direct link between the Hippo and mTORC1 pathways in the control of tumour growth by regulating the activation of mTORC1 through the interaction of long noncoding RNA HPR with Raptor. Knockdown or knockout of HPR in breast cancer and cholangiocarcinoma cells led to a reduction in tumour growth, indicating the importance of this crosstalk in tumorigenesis.
CELL DEATH & DISEASE
(2021)
Article
Engineering, Biomedical
Minjeong Jang, Jinhyeon An, Seung Won Oh, Joo Yeon Lim, Joon Kim, Jung Kyoon Choi, Jae-Ho Cheong, Pilnam Kim
Summary: The stiffness of the extracellular matrix in gastric cancer cells reversibly regulates the DNA methylation of YAP, suggesting potential therapeutic strategies through epigenetic reprogramming.
NATURE BIOMEDICAL ENGINEERING
(2021)
Article
Oncology
Richard Cunningham, Siyang Jia, Krishna Purohit, Omar Salem, Ning Sze Hui, Yue Lin, Neil O. Carragher, Carsten Gram Hansen
Summary: The dysregulation of the Hippo signaling pathway is common in various types of cancer. This study investigates the relationship between the most prevalent driver mutations in pleural mesothelioma (PM) and disruption of the Hippo pathway, while assessing correlations with clinical markers. The findings suggest that patients with transcriptional markers of YAP/TAZ activation have a worse prognosis, indicating the potential of using Hippo pathway transcriptional activation status for patient stratification.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Biochemical Research Methods
Loan Vulliard, Joel Hancock, Anton Kamnev, Christopher W. Fell, Joana Ferreira da Silva, Joanna Loizou, Vanja Nagy, Loic Dupre, Joerg Menche
Summary: BioProfiling.jl is an efficient end-to-end solution for compiling and filtering informative morphological profiles in Julia. It provides necessary data structures and helper functions for analyzing and visualizing profiles, as well as robust statistical methods for quantifying the significance of observed changes. By analyzing a chemical imaging screen, this package demonstrates the informative nature of morphological profiles in understanding compound mechanisms of action.
Article
Medicine, Research & Experimental
Ruize Gao, Ravi K. R. Kalathur, Mairene Coto-Llerena, Caner Ercan, David Buechel, Song Shuang, Salvatore Piscuoglio, Michael T. Dill, Fernando D. Camargo, Gerhard Christofori, Fengyuan Tang
Summary: The study reveals the critical role of YAP/TAZ in suppressing ferroptosis and establishing Sorafenib resistance in hepatocellular carcinoma (HCC). This highlights YAP/TAZ-based rewiring strategies as potential approaches to overcome HCC therapy resistance. The findings provide new insights into improving the efficacy of current therapies in cancer treatment.
EMBO MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Jakob Haldrup, Siri H. Strand, Clara Cieza-Borrella, Magnus E. Jakobsson, Maria Riedel, Maibritt Norgaard, Stine Hedensted, Frederik Dagnaes-Hansen, Benedicte Parm Ulhoi, Rosalind Eeles, Michael Borre, Jesper Olsen, Martin Thomsen, Zsofia Kote-Jarai, Karina D. Sorensen
Summary: FRMD6 has been identified as a novel tumor suppressor gene and prognostic biomarker candidate in prostate cancer, with its low expression associated with postoperative biochemical recurrence. It inhibits functions and growth of PC cells, leading to enrichment of Hippo/YAP and c-MYC signaling pathways upon knockout, ultimately causing prostatic intraepithelial neoplasia and hyperproliferation.
Article
Oncology
Sojung Han, Ji Yeon Lim, Kyungjoo Cho, Hye Won Lee, Jun Yong Park, Simon Weonsang Ro, Kyung Sik Kim, Haeng Ran Seo, Do Young Kim
Summary: The activation of YAP/TAZ is associated with the development of liver cancer, and their expression level is known to relate to chemoresistance. However, the therapeutic effects of YAP/TAZ inhibition combined with sorafenib and conventional chemotherapy in hepatocellular carcinoma (HCC) are still unclear. This study aimed to assess the YAP/TAZ expression level in HCCs and investigate the therapeutic effects of CA3 (a novel YAP inhibitor) combined with sorafenib using a patient-derived multicellular tumor spheroid (MCTS) model. The results showed that patient-derived MCTS with high YAP/TAZ expression responded more sensitively to the combination therapy than those with low or medium YAP/TAZ expression, suggesting that YAP/TAZ inhibition could enhance sensitivity to sorafenib in HCCs with high YAP/TAZ expression.
Article
Medicine, General & Internal
Li Liu, Ziyang Lu, Xiayun Hu, Tianyuan Su, Liping Su, Hongwei Pu
Summary: The study found that the proteins YAP1 and TAZ are highly expressed in esophageal squamous cell carcinoma (ESCC) and closely related to clinical and pathological parameters of the tumor. They may be involved in the development of ESCC and can be used as prognostic markers.
Article
Oncology
Xiaopeng Chen, Xiaowei Zhang, Yitong Jiang, Xuemei Zhang, Min Liu, Shanna Wang, Shaoqiong Liu, Haiyan Liang, Chunhua Liu
Summary: In this study, researchers found that low shear stress activated Yes-associated protein (YAP1) and led to its localization in the nucleus of renal cell carcinoma (RCC) cells. Inhibition of ROCK or RhoA partially prevented YAP1 accumulation in the nucleus. Targeting YAP1 activation decreased low shear stress-induced epithelial-mesenchymal transition (EMT), as well as the expression of N-cadherin, SNAIL1, and TWIST. Salvianolic acid B inhibited YAP1 and Hippo signaling activation, and prevented low shear stress-induced EMT.
Review
Biology
Hyunjung Park, Hyerin Park, Jiyeon Baek, Hyuk Moon, Simon Weonsang Ro
Summary: Hepatocellular carcinoma (HCC) is a significant global health issue with increasing incidence. Current treatment strategies for HCC primarily target receptor tyrosine kinases (RTKs) and immune checkpoint regulators. However, the clinical outcomes of these therapies have been unsatisfactory, leading to the exploration of novel molecular target therapies, including YAP/TAZ, Hedgehog, and Wnt/β-catenin signaling pathways.
