The monoamine oxidase-A inhibitor clorgyline promotes a mesenchymal-to-epithelial transition in the MDA-MB-231 breast cancer cell line

Satram-Maharaj, Tamara; Nyarko, Jennifer N.K.; Kuski, Kelly; Fehr, Kelsey; Pennington, Paul R.; Truitt, Luke; Freywald, Andrew; Lukong, Kiven Erique; Anderson, Deborah H.; Mousseau, Darrell D.

doi:10.1016/j.cellsig.2014.08.005

Cited by 23 publications

(19 citation statements)

References 41 publications

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“…Few studies have shown re-expression of the molecule in metastatic breast and prostate carcinomas 16–19. Similar observations were also made in vitro 20 21. Moreover, the expression of E-cadherin in metastatic prostate carcinoma was found to inversely correlate with the size of metastatic deposits, an observation thought to readily allow for a second EMT at a distant site 17.…”

Section: Introductionsupporting

confidence: 73%

Reacquisition of E-cadherin expression in metastatic deposits of signet-ring cell carcinoma of the upper gastrointestinal system: a potential anchor for metastatic deposition

2016

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While the reduction of E-cadherin in primary SRCC supports its pivotal role in epithelial-mesenchymal transition, a process crucial in tumour progression and metastatic dissemination, the re-expression of this molecule in metastatic SRCC cells implies a reversal to their epithelial phenotype (thus mesenchymal-epithelial transition) which, in turn, theoretically helps tumour cells to anchor and form cohesive metastatic deposits.

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Section: Introductionsupporting

confidence: 73%

Reacquisition of E-cadherin expression in metastatic deposits of signet-ring cell carcinoma of the upper gastrointestinal system: a potential anchor for metastatic deposition

2016

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“…In this study MAOA inhibitor treatment effectively restricted PCa metastasis and prolonged mouse survival. However, MAOA inhibitors were reported to promote EMT in breast cancer cells (Satram-Maharaj et al, 2014). These controversial results suggest that the role of MAOA-associated signaling networks during cancer progression may be context dependent.…”

Section: Pharmacological Maoa Inhibition Reduces Metastasis By Disrupmentioning

confidence: 99%

MAOA-Dependent Activation of Shh-IL6-RANKL Signaling Network Promotes Prostate Cancer Metastasis by Engaging Tumor-Stromal Cell Interactions

et al. 2017

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Metastasis is a predominant cause of death for prostate cancer (PCa) patients; however, the underlying mechanisms are poorly understood. We report that monoamine oxidase A (MAOA) is a clinically and functionally important mediator of PCa bone and visceral metastases, activating paracrine Shh signaling in tumor-stromal interactions. MAOA provides tumor cell growth advantages in the bone microenvironment by stimulating interleukin-6 (IL6) release from osteoblasts, and triggers skeletal colonization by activating osteoclastogenesis through osteoblast production of RANKL and IL6. MAOA inhibitor treatment effectively reduces metastasis and prolongs mouse survival by disengaging the Shh-IL6-RANKL signaling network in stromal cells in the tumor microenvironment. These findings provide a rationale for targeting MAOA and its associated molecules to treat PCa metastasis.

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“…However, recent studies have shown that E-cadherin expression might be also modulated at a posttranscriptional level 1 . Although the level of E-cadherin expression is significantly decreased or even no during tumorigenesis, tumor cells still contain considerable amount of E-cadherin mRNA 14 15 . The disparity between E-cadherin protein and mRNA levels in metastatic tumor cells was also confirmed by our experiment of overexpressing E-cadherin protein in metastatic tumor cells, in which no E-cadherin protein was produced while E-cadherin mRNA was overexpressed (Zen et al , unpublished).…”

mentioning

confidence: 99%

Slug-upregulated miR-221 promotes breast cancer progression through suppressing E-cadherin expression

Pan

Zhang

et al. 2016

Sci Rep

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It is generally regarded that E-cadherin is downregulated during tumorigenesis via Snail/Slug-mediated E-cadherin transcriptional reduction. However, this transcriptional suppressive mechanism cannot explain the failure of producing E-cadherin protein in metastatic breast cancer cells after overexpressing E-cadherin mRNA. Here we reveal a novel mechanism that E-cadherin is post-transcriptionally regulated by Slug-promoted miR-221, which serves as an additional blocker for E-cadherin expression in metastatic tumor cells. Profiling the predicted E-cadherin-targeting miRNAs in breast cancer tissues and cells showed that miR-221 was abundantly expressed in breast tumor and metastatic MDA-MB-231 cells and its level was significantly higher in breast tumor or MDA-MB-231 cells than in distal non-tumor tissue and low-metastatic MCF-7 cells, respectively. MiR-221, which level inversely correlated with E-cadherin level in breast cancer cells, targeted E-cadherin mRNA open reading frame (ORF) and suppressed E-cadherin protein expression. Depleting or increasing miR-221 level in breast cancer cells induced or decreased E-cadherin protein level, leading to suppressing or promoting tumor cell progression, respectively. Moreover, miR-221 was specifically upregulated by Slug but not Snail. TGF-β treatment enhanced Slug activity and thus increased miR-221 level in MCF-7 cells. In summary, our results provide the first evidence that Slug-upregulated miR-221 promotes breast cancer progression via reducing E-cadherin expression.

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The monoamine oxidase-A inhibitor clorgyline promotes a mesenchymal-to-epithelial transition in the MDA-MB-231 breast cancer cell line

Cited by 23 publications

References 41 publications

Reacquisition of E-cadherin expression in metastatic deposits of signet-ring cell carcinoma of the upper gastrointestinal system: a potential anchor for metastatic deposition

Reacquisition of E-cadherin expression in metastatic deposits of signet-ring cell carcinoma of the upper gastrointestinal system: a potential anchor for metastatic deposition

MAOA-Dependent Activation of Shh-IL6-RANKL Signaling Network Promotes Prostate Cancer Metastasis by Engaging Tumor-Stromal Cell Interactions

Slug-upregulated miR-221 promotes breast cancer progression through suppressing E-cadherin expression

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