FAM83A Promotes Lung Cancer Progression by Regulating the Wnt and Hippo Signaling Pathways and Indicates Poor Prognosis

Zheng, Yiwen; Li, Zhi-Han; Lei, Lei; Liu, Chenchen; Wang, Zhao; Fei, Liangru; Yang, Mingyong; Huang, Wenjing; Xu, Hong‐Tao

doi:10.3389/fonc.2020.00180

Cited by 57 publications

(56 citation statements)

References 35 publications

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“…Wnt/β-catenin was found to physically activate YAP signaling in HEK293 cells in a previous study [ 109 ]. Another recent study showed that the concurrent activation of Wnt/β-catenin and YAP signaling promotes cancer progression and is associated with poor prognosis in NSCLC [ 110 ]. A previous study demonstrated that YAP forms a positive feedback loop with the Notch and Wnt/β-catenin signaling pathways to promote liver tumorigenesis, and Hippo kinases repress this loop [ 111 ].…”

Section: Hippo/yap Singing Pathway In Nsclcmentioning

confidence: 99%

“…The regulation of the Hippo kinase cascade, YAP, and other signaling pathways is complex. Previous studies have shown that signaling pathways, including MAPK, PI3K, Wnt, TGFβ, Notch, and Hh, directly activate YAP to form a positive loop in part and partly activate YAP by repressing Hippo kinases [ 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 109 , 110 , 111 , 112 , 113 ]. Loss of function or mutations in Hippo kinases, including NF2 and LATS1/2, lead to the activation of YAP, and then YAP activation positively interacts with other signaling pathways to promote cancer progression [ 114 , 115 , 116 ].…”

Section: Hippo/yap Singing Pathway In Nsclcmentioning

confidence: 99%

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The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)

Hsu

Yang

Jablons

et al. 2020

Cancers

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The advancement of new therapies, including targeted therapies and immunotherapies, has improved the survival of non-small-cell lung cancer (NSCLC) patients in the last decade. Some NSCLC patients still do not benefit from therapies or encounter progressive disease during the course of treatment because they have intrinsic resistance, acquired resistance, or lack a targetable driver mutation. More investigations on the molecular biology of NSCLC are needed to find useful biomarkers for current therapies and to develop novel therapeutic strategies. Src is a non-receptor tyrosine kinase protein that interacts with cell surface growth factor receptors and the intracellular signaling pathway to maintain cell survival tumorigenesis in NSCLC. The Yes-associated protein (YAP) is one of the main effectors of the Hippo pathway and has been identified as a promoter of drug resistance, cancer progression, and metastasis in NSCLC. Here, we review studies that have investigated the activation of YAP as mediated by Src kinases and demonstrate that Src regulates YAP through three main mechanisms: (1) direct phosphorylation; (2) the activation of pathways repressing Hippo kinases; and (3) Hippo-independent mechanisms. Further work should focus on the efficacy of Src inhibitors in inhibiting YAP activity in NSCLC. In addition, future efforts toward developing potentially reasonable combinations of therapy targeting the Src–YAP axis using other therapies, including targeted therapies and/or immunotherapies, are warranted.

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Section: Hippo/yap Singing Pathway In Nsclcmentioning

confidence: 99%

Section: Hippo/yap Singing Pathway In Nsclcmentioning

confidence: 99%

The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)

Hsu

Yang

Jablons

et al. 2020

Cancers

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“…Calculating studies revealed the mechanisms of FAM83A in various cancers. Zheng YW et al (8) found that FAM83A…”

Section: Discussionmentioning

confidence: 99%

“…Recently, increasing studies have found that dysregulated FAM83A is a potential biomarker in various cancers, including breast, hepatocellular and lung adenocarcinoma cancers (7; 8; 9; 10; 11; 12) . It was reported that FAM83A promotes lung adenocarcinoma cancer progression by regulating the Wnt and Hippo (8) and ERK and PI3K/Akt/mTOR pathways (13) , making it a promising therapeutic target. Besides, circ-ZKSCAN1/miR-330-5p/FAM83A feedback loop plays important role in promoting the progress of NSCLC (14) .…”

Section: Introductionmentioning

confidence: 99%

Family With Sequence Similarity 83, Member A (FAM83A) As a Promising Prognostic Biomarker in Lung Squamous Cell Cancer

Wang¹,

Lu²,

Feng³

et al. 2020

Preprint

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Background: Increasing studies have found the dysregulated FAM83A as a potential biomarker in various cancers. Its function in cancer cells is largely unknown, and especially their role in LUSC remains unclear. We detected the expression level and prognosis role of FAM83A in LUSC.Methods: The bioinformatics methods were performed initially to predict the expression level and prognostic value of FAM83A mRNA in LUSC. We used IHC to examine its protein expression level and identify its prognostic value using 132 pairs of tissues.Results: Results from TCGA and Oncomine databases revealed that FAM83A mRNA expression level was significantly higher in LUSC than that in normal lung tissue. TCGA and GEO databases revealed FAM83A mRNA overexpression was significantly associated with poorer OS of LUSC patients (all P<0.05). Furtherly, our IHC results revealed that FAM83A was overexpressed in 78 (59.1%) patients and 19(14.4%) pancancerous tissues (P<0.001). Kaplan-Meier analyses revealed that high FAM83A protein expression was significantly associated with decreased 5-years’ OS (P = 0.007) and PFS (P = 0.007). Via multivariate analysis, FAM83A expression level was independent prognostic factor for both OS (P = 0.006) and PFS (P = 0.002).Conclusion: FAM83A was overexpressed in LUSC and it could serve as a prognosis prediction biomarker for LUSC. FAM83A could act as one new potential therapeutic target for LUSC treatment.

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“…Also, FAM83A-S1 could promote the progression of lung cancer through the FAM83A/ERK pathway [16]. Recent studies have shown that FAM83A also interacts with Wnt and Hippo signaling pathway [17].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of FAM83A Promotes Proliferation and Metastasis Via Activating Wnt/β-catenin Signaling Pathway in Head Neck Squamous Cell Carcinoma

Huan¹,

Song²,

Zhang³

et al. 2020

Preprint

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Purpose:This research aimed to investigate FAM83A expression in head and neck squamous cell carcinoma (HNSCC) and its function in the proliferation and metastasis.Materials and Methods:FAM83A mRNA and protein expression in HNSCC was detected via TCGA database, primary HNSCC samples, and cell lines. The associations between FAM83A expression and clinicopathologic variables were evaluated through tissue microarrays. Besides, FAM83A knockdown and overexpression cell lines were constructed to assess its biological function including cell growth and metastasis in vitro and the relationship between FAM83A and epithelial-mesenchymal transition (EMT) was explored. Furthermore, two models of xenograft tumors in nude mice were used to assess the tumorigenicity and metastasis ability of FAM83A in vivo.Results:In the present study, we discovered the FAM83A expression was overexpressed in the HNSCC samples and was significantly associated with tumor size, lymph node status, and pathological grades. Mechanically, FAM83A could promote HNSCC cell growth and metastasis by inducing EMT via activating Wnt/β-catenin signaling pathway. Rescue experiment demonstrated the inhibition of β-catenin could counteract FAM83A function and there is a bi-directional signaling loop between FAM83A and Wnt/β-catenin signaling pathways. Also, the FAM83A knockdown could suppress tumor growth and distant metastasis in HNSCC xenograft animal models.Conclusions:Taken together, we demonstrated that FAM83A is upregulated in HNSCC and it could promote cell growth and metastasis via activating Wnt/β-catenin pathway in HNSCC, which may provide a novel therapeutic target in HNSCC treatment.

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FAM83A Promotes Lung Cancer Progression by Regulating the Wnt and Hippo Signaling Pathways and Indicates Poor Prognosis

Cited by 57 publications

References 35 publications

The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)

The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)

Family With Sequence Similarity 83, Member A (FAM83A) As a Promising Prognostic Biomarker in Lung Squamous Cell Cancer

Overexpression of FAM83A Promotes Proliferation and Metastasis Via Activating Wnt/β-catenin Signaling Pathway in Head Neck Squamous Cell Carcinoma

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