Depression promotes prostate cancer invasion and metastasis via a sympathetic-cAMP-FAK signaling pathway

Cheng, Yan; Gao, Xinghua; Li, Xian-Jing; Cao, Qiu-Hua; Zhao, Dandan; Zhou, Jin‐Rong; Wu, Hongxi; Wang, Yun; Li, You; Yang, Hongbao; He, Yunlong; Li, Yongren; Bian, Jin-Song; Zhu, Qingyi; Birnbaumer, Lutz; Yang, Yong

doi:10.1038/s41388-018-0177-4

Cited by 57 publications

(50 citation statements)

References 56 publications

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“…To further observe the relationship between the target circRNA and OSCC development, we conducted KEGG pathway analysis using sequencing data and bioinformatics technology. Pathway analysis results showed that many items corresponded to cancer, such as the cAMP signaling pathway, proteoglycans in cancer, and the AMPK signaling pathway [24][25][26][27]. The AMPK pathway has been found to be related to OSCC progression [28].…”

Section: Discussionmentioning

confidence: 99%

“…KEGG results suggested that the top 20 of KEGG enrichment terms are correlated with cancer development (Figure 6A, 6B). Among these items, were tumor-correlated, such as the cAMP signaling pathway, proteoglycans in cancer, and the AMPK signaling pathway [24][25][26][27]. Furthermore, AMPK signaling pathway has been discovered to be correlated with OSCC progression [28].…”

Section: Functional Enrichment Analyses Of Hsa_circ_0086414 Gene and mentioning

confidence: 99%

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Hsa_circ_0086414 Might Be a Diagnostic Biomarker of Oral Squamous Cell Carcinoma

Zhang

2020

Med Sci Monit

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Departmental sources Background: Circular RNAs (circRNAs), a newly-discovered class of non-coding RNAs, have a significant role in the progression of cancers, but the effect of hsa_circ_0086414 in human oral squamous cell carcinoma (OSCC) is still unclear. Material/Methods: The circRNAs expression profile in OSCC tissue samples was assessed by high-throughput sequencing. The hsa_circ_0086414 expression level in 55 paired OSCC tissue samples and 2 kinds of OSCC cells was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the correlation between the hsa_circ_0086414 expression and clinicopathological characteristics of individuals with OSCC was studied. We used receiver operating characteristic (ROC) curves to observe the hsa_circ_0086414 value of diagnosis in OSCC. The network of hsa_circ_0086414-miRNAs-mRNAs was constructed. Gene Ontology (GO), Disease Oncology (DO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out based on sequencing data and bioinformatics predictions. Results: Hsa_circ_0086414 expression in OSCC tissue samples and OSCC cells was first discovered to be significantly downregulated compared with the adjacent healthy tissues (AHTs) and normal (HaCaT) cells, respectively. Moreover, its expression level was significantly correlated with stage in TNM, size of tumor, and lymph node metastasis. The area below the ROC curve was 0.749. Hsa_circ_0086414-miRNAs-mRNAs network analysis and GO, DO, and KEGG analyses all demonstrated that hsa_circ_0086414 is correlated with cancer progression to a certain extent. Conclusions: We discovered that hsa_circ_0086414 might be an essential diagnostic biomarker in OSCC. Furthermore, hsa_circ_0086414 could be a target for OSCC therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Functional Enrichment Analyses Of Hsa_circ_0086414 Gene and mentioning

confidence: 99%

Hsa_circ_0086414 Might Be a Diagnostic Biomarker of Oral Squamous Cell Carcinoma

Zhang

2020

Med Sci Monit

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“…S4C, the fourth cell pathway under 2 μM ADT-OH treatment is cell adhesion. It is well known that the FAK signaling pathway plays a crucial role in the metastasis and invasion of a variety of tumor cells (20)(21)(22). Here, we found that FAK is involved in multiple signaling pathways including cell migration following ADT-OH treatment ( Fig.…”

Section: Adt-oh Inhibits Cell Migration By Regulating Fak Signaling Pmentioning

confidence: 57%

ADT-OH exhibits anti-metastatic activity on malignant melanoma through inhibition of FAK/Paxillin signaling pathways

Cai

et al. 2020

Preprint

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Background: Melanoma is a highly aggressive cancer, and its high metastasis results in a high lethality. Hydrogen sulfide (H2S) is now widely recognized as the third endogenous gas delivery substance and may play a key role in cancer biological processes. The present study was designed to evaluate the anti-metastatic effect of H2S-donor ADT-OH on melanoma cells and the underlying mechanism.Methods: Firstly, the effect of ADT-OH on the migration of melanoma cells was explored in vivo by the mouse footpad injection model and the mouse tail vein metastasis model. Tumor xenograft growth and tumor tissue H&E analyses were also measured in vivo. Then, the migration inhibitory effect and the underlying mechanism of ADT-OH on B16F10, B16F1 and A375 melanoma cell lines were evaluated by wound healing, transwell, western blot and immunofluorescence analyses. Results: Our data showed that ADT-OH inhibited the migration and invasion of melanoma cells significantly in vivo in three different animal models. Further research showed that ADT-OH significantly suppressed the migratory, invasive and adhesive properties of A375 and B16F10 cells as measured by the wound-healing and transwell assays. Mechanistically, ADT-OH treatment suppressed the EMT processes and reduced the enzymatic activity of FAK and Paxillin. Moreover, abnormal CSE/CBS and AKT signaling pathways in A375 and B16F10 cells were notably observed following ADT-OH treatment. Additionally, ADT-OH at higher concentration significantly inhibited the proliferation of highly metastatic melanoma A375 and B16F10 cells.Conclusions: Our results suggest that ADT-OH exerts anti-metastasis activity in melanoma cells by suppressing the EMT process through the CSE/CBS and FAK signaling pathways, and it might be used as an agent against metastatic melanoma in future.

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“…We thus inferred that high cAMP levels increase MOB2 expression in GBM cells, resulting in more MOB2 binding to PKA and subsequent enhanced PKA activation, whereas low cAMP levels achieve opposite effects. As the cAMP/PKA signaling is known to inhibit cell migration and invasion [26][27][28][29][30] , we suggest cAMP level-regulated MOB2 as a novel regulator in cAMP/PKA signaling-mediated effects on GBM cell migration and invasion.…”

Section: Discussionmentioning

confidence: 84%

“…The cAMP/PKA signaling has been shown to suppress cell migration and invasion 25 , which involves the inactivation of FAK/Akt [26][27][28][29][30] . We further examined whether FSK affects the activation of FAK/Akt in LN-229 and T98G cells stably depleted MOB2 with two distinct shRNAs.…”

Section: Mob2 Plays a Role In Camp/pka-mediated Inhibition Of Cell MImentioning

confidence: 99%

MOB2 suppresses GBM cell migration and invasion via regulation of FAK/Akt and cAMP/PKA signaling

Jiang

Yao

et al. 2020

Cell Death Dis

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Mps one binder 2 (MOB2) regulates the NDR kinase family, however, whether and how it is implicated in cancer remain unknown. Here we show that MOB2 functions as a tumor suppressor in glioblastoma (GBM). Analysis of MOB2 expression in glioma patient specimens and bioinformatic analyses of public datasets revealed that MOB2 was downregulated at both mRNA and protein levels in GBM. Ectopic MOB2 expression suppressed, while depletion of MOB2 enhanced, the malignant phenotypes of GBM cells, such as clonogenic growth, anoikis resistance, and formation of focal adhesions, migration, and invasion. Moreover, depletion of MOB2 increased, while overexpression of MOB2 decreased, GBM cell metastasis in a chick chorioallantoic membrane model. Overexpression of MOB2-mediated antitumor effects were further confirmed in mouse xenograft models. Mechanistically, MOB2 negatively regulated the FAK/Akt pathway involving integrin. Notably, MOB2 interacted with and promoted PKA signaling in a cAMPdependent manner. Furthermore, the cAMP activator Forskolin increased, while the PKA inhibitor H89 decreased, MOB2 expression in GBM cells. Functionally, MOB2 contributed to the cAMP/PKA signaling-regulated inactivation of FAK/Akt pathway and inhibition of GBM cell migration and invasion. Collectively, these findings suggest a role of MOB2 as a tumor suppressor in GBM via regulation of FAK/Akt signaling. Additionally, we uncover MOB2 as a novel regulator in cAMP/PKA signaling. Given that small compounds targeting FAK and cAMP pathway have been tested in clinical trials, we suggest that interference with MOB2 expression and function may support a theoretical and therapeutic basis for applications of these compounds.

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Depression promotes prostate cancer invasion and metastasis via a sympathetic-cAMP-FAK signaling pathway

Cited by 57 publications

References 56 publications

Hsa_circ_0086414 Might Be a Diagnostic Biomarker of Oral Squamous Cell Carcinoma

Hsa_circ_0086414 Might Be a Diagnostic Biomarker of Oral Squamous Cell Carcinoma

ADT-OH exhibits anti-metastatic activity on malignant melanoma through inhibition of FAK/Paxillin signaling pathways

MOB2 suppresses GBM cell migration and invasion via regulation of FAK/Akt and cAMP/PKA signaling

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