Downregulation of Snail by DUSP1 Impairs Cell Migration and Invasion through the Inactivation of JNK and ERK and Is Useful as a Predictive Factor in the Prognosis of Prostate Cancer

Martínez-Martínez, Desirée; Lobo, M. Toledo; Baquero, Pablo; Ropero, Santiago; Angulo, Javier C.; Chiloeches, Antonio; Lasa, Marina

doi:10.3390/cancers13051158

Cited by 17 publications

(10 citation statements)

References 61 publications

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“…As shown in Figure 4A, there was no change in p38 and JNK signaling pathway, indicating a specific relationship with the ERK/MARK pathway. According to the previous studies, DUSPs can inactivate ERK1, 2 by dephosphorylating residues required for catalytic activity (Chappell et al, 2013;Ramkissoon et al, 2019;Martínez-Martínez et al, 2021). Then we selected the differential genes DUSP3/DUSP4/DUSP6 related to ERK dephosphorylation in the ERK/MAPK pathway and performed RT-qPCR to examine the expression of DUSP3/DUSP4/DUSP6 in control and hnRNPA2B1-KO cell lines.…”

Section: Hnrnpa2b1 Promotes the Development Of Colon Cancer By Regulating The Erk/mapk Pathwaymentioning

confidence: 99%

hnRNPA2B1 Promotes Colon Cancer Progression via the MAPK Pathway

et al. 2021

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HNRNPA2B1, an RNA-binding protein, plays a key role in primary microRNA processing, alternative splicing, mRNA metabolism and transport. Interestingly, hnRNPA2B1 also works as an N6-methyladenosine (m6A) reader and is critical during tumorigenesis of various tissue types. However, its role in colon cancer is still unclear. In this study, we aimed to elucidate the biological functions of hnRNPA2B1 and to explore its underlying mechanisms in colon cancer. We examined the expression of hnRNPA2B1 in Oncomine and TCGA databases. Then verified the findings in colon cancer cells and clinical samples with western blotting and immunohistochemistry (IHC). We used CRISPR/Cas9 directed gene editing to knockout hnRNPA2B1 expression in human colon cancer cell line SW480 and HCT-116 and carried out both in vivo and in vitro experiments. The results were further confirmed by RNA-seq analyses. We found that hnRNPA2B1 significantly promoted colon cancer cell proliferation both in vitro and in vivo, while knockout of hnRNPA2B1 induced apoptosis and cell cycle arrest in SW480. RNA-seq analyses revealed that the ERK/MAPK pathway was activated by hnRNPA2B1 upregulation. In addition, both hnRNPA2B1 and MAPK pathway were activated in clinical colon cancer specimens and positively correlated. Mechanistically, hnRNPA2B1 appeared to be an upstream regulator of the ERK/MAPK pathway and inhibition of MAPK signaling blocked the effects of hnRNPA2B1. Taken together, our data demonstrated that the RNA-binding protein hnRNPA2B1 promotes cell proliferation and regulates cell cycle and apoptosis of human colon cancer by activating the ERK/MAPK signaling, which may provide a new insight into the development of hnRNPA2B1 as a potential therapeutic target for treatment of colon cancer.

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Section: Hnrnpa2b1 Promotes the Development Of Colon Cancer By Regulating The Erk/mapk Pathwaymentioning

confidence: 99%

hnRNPA2B1 Promotes Colon Cancer Progression via the MAPK Pathway

et al. 2021

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“…As several of these studied signaling pathways are also involved in cell migration[ 46 ], we then decided to study this process. As shown in Figure 2 , we observed that PTHrP enhances the motility of CRC-derived cell lines[ 40 ].…”

Section: Pthrp Promotes Cell Cycle Progression Proliferation and Migration Of Crc Cellsmentioning

confidence: 99%

Involvement of parathyroid hormone-related peptide in the aggressive phenotype of colorectal cancer cells

Díaz¹,

Carriere²,

Martín³

et al. 2021

WJG

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Colorectal cancer (CRC) remains one of the leading causes of mortality from malignant diseases worldwide. In general terms, CRC presents high heterogeneity due to the influence of different genetic and environmental factors; also, the neoplastic cells are strongly influenced by the extracellular matrix and several surrounding cells, known together as the tumor microenvironment (TME). Bidirectional communication takes place between the tumor and the TME through the release of autocrine and paracrine factors. Parathyroid hormone-related peptide (PTHrP) is a cytokine secreted by a wide variety of tissues and is able to regulate several cellular functions both in physiological as well as in pathological processes. It exerts its effects as a paracrine/autocrine factor, although its mode of action is mainly paracrine. It has been shown that this peptide is expressed by several tumors and that the tumor secretion of PTHrP is responsible for the malignant humoral hypercalcemia. Eight years ago, when our research group started studying PTHrP effects in the experimental models derived from intestinal tumors, the literature available at the time addressing the effects of PTHrP on colorectal tumors was limited, and no articles had been published regarding to the paracrine action of PTHrP in CRC cells. Based on this and on our previous findings regarding the role of PTH in CRC cells, our purpose in recent years has been to explore the role of PTHrP in CRC. We analyzed the behavior of CRC cells treated with exogenous PTHrP, focalizing in the study of the following events: Survival, cell cycle progression and proliferation, migration, chemoresistance, tumor-associated angiogenesis, epithelial to mesenchymal transition program and other events also associated with invasion, such us the induction of cancer stem cells features. This work summarizes the major findings obtained by our investigation group using in vitro and in vivo CRC models that evidence the participation of PTHrP in the acquisition of an aggressive phenotype of CRC cells and the molecular mechanisms involved in these processes. Recently, we found that this cytokine induces this malignant behavior not only by its direct action on these intestinal cells but also through its influence on cells derived from TME, promoting a communication between CRC cells and surrounding cells that contributes to the molecular and morphological changes observed in CRC cells. These investigations establish the basis for our next studies in order to address the clinical applicability of our findings. Recognizing the factors and mechanisms that promote invasion in CRC cells, evasion to the cytotoxic effects of current CRC therapies and thus metastasis is decisive for the identification of new markers with the potential to improve early diagnosis and/or to predict prognosis, to predetermine drug resistance and to provide treatment guidelines that include targeted therapies for this disease.

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“…More recently, it has been shown that TRβ is also able to limit the CSCs population in breast cancer by decreasing, not only their self-renewal capacity, but also the efficiency of mammosphere formation as well as the expression of pluripotency factors ( 114 ). Different reports have demonstrated that mammospheres are enriched in EMT markers such as the transcription factor Snail ( 115 – 117 ), which is constitutively upregulated in a wide variety of tumors ( 118 ), including prostate cancer ( 119 ), where NF-kB and p38MAPK signaling pathways play important roles ( 46 ). Despite this, TRβ increases Snail expression in mammospheres, suggesting that the effects of T3 on CSC biology are not related to EMT changes ( 114 ).…”

Section: Introductionmentioning

confidence: 99%

Thyroid hormones act as modulators of inflammation through their nuclear receptors

Lasa

Contreras‐Jurado

2022

Front. Endocrinol.

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Reciprocal crosstalk between endocrine and immune systems has been well-documented both in physiological and pathological conditions, although the connection between the immune system and thyroid hormones (THs) remains largely unclear. Inflammation and infection are two important processes modulated by the immune system, which have profound effects on both central and peripheral THs metabolism. Conversely, optimal levels of THs are necessary for the maintenance of immune function and response. Although some effects of THs are mediated by their binding to cell membrane integrin receptors, triggering a non-genomic response, most of the actions of these hormones involve their binding to specific nuclear thyroid receptors (TRs), which generate a genomic response by modulating the activity of a great variety of transcription factors. In this special review on THs role in health and disease, we highlight the relevance of these hormones in the molecular mechanisms linked to inflammation upon their binding to specific nuclear receptors. In particular, we focus on THs effects on different signaling pathways involved in the inflammation associated with various infectious and/or pathological processes, emphasizing those mediated by NF-kB, p38MAPK and JAK/STAT. The findings showed in this review suggest new opportunities to improve current therapeutic strategies for the treatment of inflammation associated with several infections and/or diseases, such as cancer, sepsis or Covid-19 infection.

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Downregulation of Snail by DUSP1 Impairs Cell Migration and Invasion through the Inactivation of JNK and ERK and Is Useful as a Predictive Factor in the Prognosis of Prostate Cancer

Cited by 17 publications

References 61 publications

hnRNPA2B1 Promotes Colon Cancer Progression via the MAPK Pathway

hnRNPA2B1 Promotes Colon Cancer Progression via the MAPK Pathway

Involvement of parathyroid hormone-related peptide in the aggressive phenotype of colorectal cancer cells

Thyroid hormones act as modulators of inflammation through their nuclear receptors

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