Identification of Cross Talk between FoxM1 and RASSF1A as a Therapeutic Target of Colon Cancer

Blanchard, Thomas G.; Czinn, Steven J.; Banerjee, Vivekjyoti; Sharda, Neha; Bafford, Andrea C; Mubariz, Fahad; Morozov, Dennis; Passaniti, Antonino; Ahmed, Hafiz; Banerjee, Aditi

doi:10.3390/cancers11020199

Cited by 14 publications

(14 citation statements)

References 36 publications

(54 reference statements)

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“…Moreover existence of an inverse correlation between RASSF1A, a tumor suppressor of the RAS signaling pathway, and FOXM1 has been observed in the progression of colon cancer. Interestingly, a cross talk between FOXM1 transcription factor and RASSF1A ( Figure 2 ) was also revealed from this study ( 25 ). RASSF1A, which is mainly altered via hypermethylation, protein degradation and point mutation has been widely observed in various cancers such as liver, breast, colon and bladder cancer ( 26 – 28 ).…”

Section: Regulation Of Foxm1supporting

confidence: 78%

FOXM1 and Cancer: Faulty Cellular Signaling Derails Homeostasis

2021

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Forkhead box transcription factor, FOXM1 is implicated in several cellular processes such as proliferation, cell cycle progression, cell differentiation, DNA damage repair, tissue homeostasis, angiogenesis, apoptosis, and redox signaling. In addition to being a boon for the normal functioning of a cell, FOXM1 turns out to be a bane by manifesting in several disease scenarios including cancer. It has been given an oncogenic status based on several evidences indicating its role in tumor development and progression. FOXM1 is highly expressed in several cancers and has also been implicated in poor prognosis. A comprehensive understanding of various aspects of this molecule has revealed its role in angiogenesis, invasion, migration, self- renewal and drug resistance. In this review, we attempt to understand various mechanisms underlying FOXM1 gene and protein regulation in cancer including the different signaling pathways, post-transcriptional and post-translational modifications. Identifying crucial molecules associated with these processes can aid in the development of potential pharmacological approaches to curb FOXM1 mediated tumorigenesis.

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Section: Regulation Of Foxm1supporting

confidence: 78%

FOXM1 and Cancer: Faulty Cellular Signaling Derails Homeostasis

2021

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“…A recent report by Blanchard identified an integrated signaling pathway between FoxM1 and RASSF1A in metastatic colorectal cancer which might be useful as a therapeutic target for colon cancer. 26 On the contrary, acquired drug resistance is the main reason for chemotherapy failure. The current clinical standard-of-care first-line chemotherapy regimen for colon cancer is mainly based on FOLFOX, and oxaliplatin is one of the main chemotherapeutic drugs.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-19b Downregulates NR3C1 and Enhances Oxaliplatin Chemoresistance in Colon Cancer via the PI3K/AKT/mTOR Pathway

Han

Chao

Wang

et al. 2021

Clin Med Insights Oncol

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Background: Identifying the genes and signaling pathways related to chemoresistance might facilitate the development of novel therapeutic strategies for colon cancer. In this study, we aimed to investigate the biological functions and underlying mechanisms of action of miR-19b and NR3C1, as well as their effects on chemosensitivity to oxaliplatin and prognosis of colon cancer patients. Methods: Reverse transcription–polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical staining were used to analyze the expression of miR-19b and NR3C1. Dual firefly luciferase reporter gene analysis was used to identify miR-19b target genes. Associations of miR-19b and NR3C1 with survival were estimated by the Kaplan–Meier method and Cox regression analyses. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometric analysis were used to measure cell viability, cytotoxicity, cell cycle phase, and apoptosis, respectively. The effect of miR-19b on cell proliferation was investigated in vivo. Results: The miR-19b was overexpressed and NR3C1 was decreased in colon cancer tissue and cell lines (SW480 and DLD-1). The miR-19b inhibition and NR3C1 overexpression inhibited cell proliferation, and induced G1/S cell cycle blockade, apoptosis, and chemosensitivity to oxaliplatin in vitro. The miR-19b inhibition suppressed subcutaneous tumorigenesis in vivo. Increased miR-19b and decreased NR3C1 in colon cancer were correlated with poor prognosis. In addition, our results confirmed NR3C1 was directly targeted by miR-19b. Thus, miR-19b might inhibit apoptosis and enhance oxaliplatin chemoresistance via the PI3K/AKT/mTOR pathway. Conclusions: Our study revealed that miR-19b promotes cell survival and chemoresistance to oxaliplatin via the PI3K/AKT/mTOR pathway by downregulating NR3C1 in colon cancer. miR-19b and NR3C1 might be potential intervention targets for chemoresistance of colon cancer.

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“…CRC patients with synchronous metastasis at first diagnosis and those patients developing metastasis during the course of disease account often for most cancer-related deaths, because of limited treatment options [18,19,20,21,24]. Optimal treatment has not yet been defined and the majority of patients with metastatic CRC are still being managed with palliative care.…”

Section: Discussionmentioning

confidence: 99%

“…Metastatic CRC has limited treatment options and thus results in higher mortality rates compared to non-metastatic CRC [18]. The cancer cells that are able to survival in circulation, and to migrate and invade another organ, are characterized by the expression of cellular oncogenes or the loss of tumor suppressor gene function [19].…”

Section: Introductionmentioning

confidence: 99%

Down-Regulation of Cannabinoid Type 1 (CB1) Receptor and its Downstream Signaling Pathways in Metastatic Colorectal Cancer

Tutino

Caruso

Nunzio

et al. 2019

Cancers

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Changes in the regulation of endocannabinoid production, together with an altered expression of their receptors are hallmarks of cancer, including colorectal cancer (CRC). Although several studies have been conducted to understand the biological role of the CB1 receptor in cancer, little is known about its involvement in the metastatic process of CRC. The aim of this study was to investigate the possible link between CB1 receptor expression and the presence of metastasis in patients with CRC, investigating the main signaling pathways elicited downstream of CB1 receptor in colon cancer. Fifty-nine consecutive patients, with histologically proven colorectal cancer, were enrolled in the study, of which 30 patients with synchronous metastasis, at first diagnosis and 29 without metastasis. A low expression of CB1 receptor were detected in primary tumor tissue of CRC patients with metastasis and consequently, we observed an alteration of CB1 receptor downstream signaling. These signaling routes were also altered in intestinal normal mucosa, suggesting that, normal mucosa surrounding the tumor provides a realistic picture of the molecules involved in tissue malignant transformation. These observations contribute to the idea that drugs able to induce CB1 receptor expression can be helpful in order to set new anticancer therapeutic strategies.

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Identification of Cross Talk between FoxM1 and RASSF1A as a Therapeutic Target of Colon Cancer

Cited by 14 publications

References 36 publications

FOXM1 and Cancer: Faulty Cellular Signaling Derails Homeostasis

FOXM1 and Cancer: Faulty Cellular Signaling Derails Homeostasis

MicroRNA-19b Downregulates NR3C1 and Enhances Oxaliplatin Chemoresistance in Colon Cancer via the PI3K/AKT/mTOR Pathway

Down-Regulation of Cannabinoid Type 1 (CB1) Receptor and its Downstream Signaling Pathways in Metastatic Colorectal Cancer

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