LATS2 as a poor prognostic marker regulates non-small cell lung cancer invasion by modulating MMPs expression

Wu, Aibing; Mo, Yanli; Luo, Yiping; Ye, Haiyin; Mai, Zong-Jiong; Guo, Kangwen; Wang, Yuzhou; Li, Shujun; Chen, Hualin; Luo, Weiren; Yang, Zhijian

doi:10.1016/j.biopha.2016.04.008

Cited by 16 publications

(20 citation statements)

References 21 publications

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“…Study by Wu et al showed that LATS2 was downregulated in NSCLC and was inversely associated with the T classification, N classification and clinical stage. In addition, LATS2 expression was an independent prognostic indicator for NSCLC patients (28). Functional experiments demonstrated that LATS2 modulates multiple biological processes, such as cell proliferation, apoptosis, migration, metastasis, and invasion (35)(36)(37)(38).…”

Section: Lats2 Is Associated With the Effects Of Mir-650 In Nsclc Cellsmentioning

confidence: 97%

“…In this study, we selected LATS2 for further confirmation (Fig. 3A) since it has previously been reported to lowly expressed in NSCLC and be involved in NSCLC formation and progression (28,29). To confirm whether LATS2 is a direct target of miR-650, luciferase reporter assay was carried out in HEK293T cells co-transfected with miR-650 inhibitor or NC inhibitor and pGL3-LATS2-3'UTR Wt or pGL3-LATS2-3'UTR Mut.…”

Section: Lats2 Is a Direct Target Of Mir-650 In Vitromentioning

confidence: 99%

“…Functional experiments demonstrated that LATS2 modulates multiple biological processes, such as cell proliferation, apoptosis, migration, metastasis, and invasion (35)(36)(37)(38). In NSCLC, upregulation of LATS2 decreased cell migration and invasion of NSCLC (28). Moreover, resumption expression of LATS2 reduced cell growth and migration in NSCLC (29).…”

Section: Lats2 Is Associated With the Effects Of Mir-650 In Nsclc Cellsmentioning

confidence: 99%

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microRNA-605 promotes cell proliferation, migration and invasion in non-small cell lung cancer by directly targeting LATS2

Zhuang

Wang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Lung cancer is the most common cause of cancerassociated mortality for men and women worldwide. An increasing number of studies have reported that the abnormal expression of microRNAs contributes to the pathogenesis of the majority of human cancer types, including non-small cell lung cancer (NSCLC). The present study aimed to measure microRNA-650 (miR-650) expression in NSCLC and evaluate its function in NSCLC cells. Reverse transcription-quantitative polymerase chain reaction was used to determine miR-650 expression in NSCLC tissue samples and cell lines. Assays for cell proliferation, migration and invasion were performed to investigate the roles of miR-650 on NSCLC progression. Furthermore, the mechanisms underlying the effects of miR-650 on NSCLC cell growth and metastasis were determined. In the current study, miR-650 was demonstrated to be highly expressed in NSCLC tissue samples and cell lines. Inhibition of expression of miR-650 suppressed NSCLC cell proliferation, migration and invasion in vitro. Additionally, large tumor suppressor kinase 2 (LATS2) was identified as a direct target gene of miR-650 in NSCLC. LATS2 was revealed to be significantly downregulated in NSCLC tissues and was negatively correlated with miR-650 expression. Notably, LATS2 re-expression decreased NSCLC cell proliferation, migration and invasion; similar to the effects induced by miR-650 underexpression. In conclusion, the results of the current study suggest that miR-650 may serve as an oncogene by direct targeting LATS2 in NSCLC formation and progression.

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Section: Lats2 Is Associated With the Effects Of Mir-650 In Nsclc Cellsmentioning

confidence: 97%

Section: Lats2 Is a Direct Target Of Mir-650 In Vitromentioning

confidence: 99%

Section: Lats2 Is Associated With the Effects Of Mir-650 In Nsclc Cellsmentioning

confidence: 99%

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microRNA-605 promotes cell proliferation, migration and invasion in non-small cell lung cancer by directly targeting LATS2

Zhuang

Wang

et al. 2017

Experimental and Therapeutic Medicine

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“…One of the key MMPs is MMP-2, which is highly expressed in tumor tissue. The modulation of MMP-2 effectively affects tumor metastasis [ 34 , 35 ]. Our study showed that CAFs upregulated the expression of both VEGF and MMP-2, suggesting that CAFs promoted lung cancer cell metastasis by modulating metastasis-related genes.…”

Section: Discussionmentioning

confidence: 99%

Cancer-associated fibroblasts enhance metastatic potential of lung cancer cells through IL-6/STAT3 signaling pathway

et al. 2017

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Recent studies indicate that cancer-associated fibroblasts (CAFs) are involved in tumor growth, invasion and metastasis, however, the underling mechanisms remain unclear. In the present study, we investigated the role of CAFs on the metastatic potential of lung cancer cells. The stromal fibroblasts we isolated from lung cancer tissues presented CAFs characteristics with high levels of α-smooth muscle actin (α-SMA) and fibroblast-activating protein (FAP). Our data showed that the conditioned medium from cultured CAFs (CAF-CM) dramatically enhanced migration and invasion of lung cancer cells. CAF-CM induced epithelial-mesenchymal transition (EMT) by regulating the expression of EMT-associated markers E-cadherin and vimentin, and also modulated metastasis-related genes MMP-2 and VEGF both in vitro and in vivo. Further mechanistic studies demonstrated that CAFs enhanced the metastatic potential of lung cancer cells by secreting IL-6, subsequently activating of JAK2/STAT3 signaling pathway. Additionally, the inhibition of IL-6/STAT3 signaling pathway by IL-6 neutralizing antibody or specific inhibitors of JAK2/STAT3 reversed CAF-CM induced EMT and migration of lung cancer cells. Taken together, these findings revealed a novel mechanism that CAFs induced EMT and promoted metastasis of lung cancer cells through the IL-6/STAT3 signaling pathway.

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“…We observed evident differences in invasion activity between the MPM cell lines (Figure 2B ). A recent study has indicated that LATS2 negatively regulates the expression of matrix metalloproteinase-2 and -9 in non-small cell lung cancer (NSCLC) [ 41 ]. Metalloproteinases are required for cell invasion because they degrade various cell adhesions and matrices [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Hyaluronic acid enhances cell migration and invasion via the YAP1/TAZ-RHAMM axis in malignant pleural mesothelioma

et al. 2017

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Most malignant mesotheliomas (MPMs) frequently show activated forms of Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which transcriptionally regulates the receptor for hyaluronic acid-mediated motility (RHAMM). As RHAMM is involved in cell migration and invasion in various tumors, we speculated that hyaluronic acid (HA) in pleural fluid might affect the progression of mesothelioma by stimulating cell migration and invasion through RHAMM. The level of RHAMM expression was decreased by YAP1/TAZ knockdown, and conversely increased by forced expression of the active form of YAP1, suggesting that RHAMM was regulated by YAP1/TAZ in MPM cells. Cell migration and invasion were also decreased by YAP1/TAZ or RHAMM knockdown. Notably, HA treatment increased cell motility and invasion, and this was abolished by RHAMM knockdown, suggesting that HA may augment local progression of MPM cells via RHAMM. Furthermore, treatment with fluvastatin, which regulates RHAMM transcription by modulating YAP1/TAZ activity, decreased the motility and invasion of MPM cells. Collectively, these data suggest that HA is an “unfavorable” factor because it promotes malignancy in mesothelioma and that the YAP1/TAZ-RHAMM axis may have potential value as a therapeutic target for inhibition of disease progression in MPM.

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LATS2 as a poor prognostic marker regulates non-small cell lung cancer invasion by modulating MMPs expression

Cited by 16 publications

References 21 publications

microRNA-605 promotes cell proliferation, migration and invasion in non-small cell lung cancer by directly targeting LATS2

microRNA-605 promotes cell proliferation, migration and invasion in non-small cell lung cancer by directly targeting LATS2

Cancer-associated fibroblasts enhance metastatic potential of lung cancer cells through IL-6/STAT3 signaling pathway

Hyaluronic acid enhances cell migration and invasion via the YAP1/TAZ-RHAMM axis in malignant pleural mesothelioma

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