LATS1 and LATS2 suppress breast cancer progression by maintaining cell identity and metabolic state

Furth, Noa; Pateras, Ioannis S.; Rotkopf, Ron; Vlachou, Vassiliki; Rivkin, Irina; Schmitt, Ina; Bakaev, Deborah; Gershoni, Anat; Ainbinder, Elena; Leshkowitz, Dena; Johnson, Randy L.; Gorgoulis, Vassilis G.; Oren, Moshe; Aylon, Yael

doi:10.26508/lsa.201800171

Cited by 28 publications

(33 citation statements)

References 84 publications

(106 reference statements)

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“…This result is consistent with data reported in several previous studies, which observed the promoted differentiation of exogenous MSCs into ATII cells in the lung tissue in ALI mice compared with normal control mice [28], and the positive effect of inhibition of the Hippo pathway on the differentiation of MSCs into ATI cells has been demonstrated recently in other studies [29, 30]. However, several studies also found diverse roles of the Hippo pathway on the differentiation of MSCs, which depends on the disease, microenvironment, and treatment timing [31, 32]. The effects of the Hippo pathway on the differentiation of BMSCs in LPS-induced ALI mice are worth exploring in further studies.…”

Section: Discussionmentioning

confidence: 97%

Lats2-Underexpressing Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice

Liu

2019

Mediators of Inflammation

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The pathophysiology of the acute lung injury (ALI) is characterized by the damage of alveolar epithelial cells, which can be repaired by exogenous bone marrow-derived mesenchymal stem cells (BMSCs). However, the migration and differentiation abilities of BMSCs are not sufficient for the purpose, and a new approach that could strengthen the repair effects of BMSCs in ALI still needs to be clarified. We have previously proved that in vitro large tumor suppressor kinase 2- (Lats2-) underexpressing BMSCs may enhance their tissue repair effects in ALI; thus, in the present study, we tried to explore whether Lats2-underexpressing BMSCs could rescue lipopolysaccharide- (LPS-) induced ALI in vivo. BMSCs from C57BL/6 mice transfected with Lats2-interfering lentivirus vector or lentivirus blank controls were transplanted intratracheally into LPS-induced ALI mice. The retention and differentiation of BMSCs in the lung were evaluated by in vivo imaging, immunofluorescence staining, and Western blotting. The lung edema and permeability were assessed by lung wet weight/body weight ratio (LWW/BW) and measurements of proteins in bronchoalveolar lavage fluid (BALF) using ELISA. Acute lung inflammation was measured by the cytokines in the lung homogenate and BALF using RT-qPCR and ELISA, respectively. Lung injury was evaluated by HE staining and lung injury scoring. Pulmonary fibrosis was evaluated by Picrosirius red staining, immunohistochemistry for α-SMA and TGF-β1, and hydroxyproline assay and RT-qPCR for Col1α1 and Col3α1. Lats2-mediated inhibition of the Hippo pathway increased the retention of BMSCs and their differentiation toward type II alveolar epithelial cells in the lung. Furthermore, Lats2-underexpressing BMSCs improved lung edema, permeability of the lung epithelium, and lung inflammation. Finally, Lats2-underexpressing BMSCs alleviated lung injury and early pulmonary fibrosis. Our studies suggest that underexpression of Lats2 could further enhance the repair effects of BMSCs against epithelial impair and the therapeutic potential of BMSCs in ALI mice.

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Section: Discussionmentioning

confidence: 97%

Lats2-Underexpressing Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice

Liu

2019

Mediators of Inflammation

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“…LATS2 is a member of the LATS tumor suppressor gene family, which significantly contributes to cancer progression and the cell cycle 28 . Studies have demonstrated the inhibitory effect of LATS2 expression in a variety of cancers 29,30 . SOCS6 is a member of the SOCS family and is mainly involved in the negative regulation of receptor tyrosine protein kinase 31 .…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circ_103820 suppresses lung cancer tumorigenesis by sponging miR-200b-3p to release LATS2 and SOCS6

et al. 2021

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A growing number of circular RNAs (circRNAs) have been identified and verified in several cancers. However, highly efficient therapeutic methods based on circRNAs in lung cancer remain largely unexplored. In the present study, we identified a novel circular RNA, hsa_circ_103820, based on Gene Expression Omnibus (GEO) data. Functionally, overexpression of hsa_circ_103820 showed significant inhibitory effects on the proliferation, migration and invasion of lung cancer cells, and knockdown of hsa_circ_103820 played promoting roles. Regarding the mechanism, we revealed that miR-200b-3p was a direct target of hsa_circ_103820 and that LATS2 and SOCS6 were the downstream target genes of miR-200b-3p. Therefore, we identified a novel potential tumor suppressive function of hsa_circ_103820 in lung cancer.

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“…The activation status of LATS2 was not examined, and whether AR is a direct substrate for LATS2 is unknown; it is, therefore, still an outstanding question if this LATS2-mediated regulation of AR transcription is phosphorylation-dependent [108]. Importantly, LATS2 levels negatively correlate with PCa tumor stage, a conserved phenomenon with several other types of carcinomas [108,109,110]. Paradoxically, LATS2 is in a range of cell types and, in vivo, a YAP/TAZ–TEAD target gene [111,112,113], which forms an integral component of a feedback loop that keeps YAP/TAZ–TEAD activity levels in check [111,112,113].…”

Section: The Hippo Pathway Promotes Castration Resistance and Metamentioning

confidence: 99%

The Hippo Pathway in Prostate Cancer

Salem

Hansen

2019

Cells

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Despite recent efforts, prostate cancer (PCa) remains one of the most common cancers in men. Currently, there is no effective treatment for castration-resistant prostate cancer (CRPC). There is, therefore, an urgent need to identify new therapeutic targets. The Hippo pathway and its downstream effectors—the transcriptional co-activators, Yes-associated protein (YAP) and its paralog, transcriptional co-activator with PDZ-binding motif (TAZ)—are foremost regulators of stem cells and cancer biology. Defective Hippo pathway signaling and YAP/TAZ hyperactivation are common across various cancers. Here, we draw on insights learned from other types of cancers and review the latest advances linking the Hippo pathway and YAP/TAZ to PCa onset and progression. We examine the regulatory interaction between Hippo-YAP/TAZ and the androgen receptor (AR), as main regulators of PCa development, and how uncontrolled expression of YAP/TAZ drives castration resistance by inducing cellular stemness. Finally, we survey the potential therapeutic targeting of the Hippo pathway and YAP/TAZ to overcome PCa.

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LATS1 and LATS2 suppress breast cancer progression by maintaining cell identity and metabolic state

Abstract: In luminal B tumors LATS2 depletion results in metabolic rewiring whereas LATS1 depletion promotes the expression of basal-like features.

Cited by 28 publications

References 84 publications

Lats2-Underexpressing Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice

Lats2-Underexpressing Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice

Circular RNA circ_103820 suppresses lung cancer tumorigenesis by sponging miR-200b-3p to release LATS2 and SOCS6

The Hippo Pathway in Prostate Cancer

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