MKK6 is Upregulated in Human Esophageal, Stomach, and Colon Cancers

Parray, Arif Ali; Baba, Rafia A.; Bhat, Hina F.; Wani, Lateef Ahmed; Mokhdomi, Taseem A.; Mushtaq, Umar; Bhat, Sehar Saleem; Kirmani, Deeba; Kuchay, Sanaullah; Wani, Mudassir Maqbool; Khanday, Firdous A.

doi:10.3109/07357907.2014.933236

Cited by 30 publications

(27 citation statements)

References 37 publications

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“…We believed that in OS, these pathways can be regulating the anti‐apoptotic signals or even the activity of cytokines and proteases which may collaborate for tumor progression and a worse outcome of OS patients. Moreover, upregulation of MAP2K6 have been described in several types of cancer …”

Section: Discussionmentioning

confidence: 99%

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MAPK pathways regulation by DUSP1 in the development of osteosarcoma: Potential markers and therapeutic targets

Lopes

Tesser-Gamba

Petrilli

et al. 2017

Molecular Carcinogenesis

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Osteosarcoma (OS) is the most frequent primary bone tumor that affect children and adolescents. This tumor is highly aggressive with high risk of metastasis and the implementation of new drugs has not been successful. The search for biomarkers or new therapeutic targets is urgently needed and can help in advances of OS treatment. MAPKs are major signaling transduction molecules that play an important role in regulating a variety of cellular responses. DUSP1 is a phosphatase that dephosphorylates the MAPKs. Both MAPKs and DUSPs have been implicated as major modulators of critical signaling pathways that are dysregulated in various diseases. In a previous study, we found an increase in MAPK7 gene expression contributed for worst overall survival and treatment response. We analyzed gene expression of MAPK pathways that participate in MAPK7 regulation, and DUSP1 gene using paired 28 pre/post-chemotherapy and 12 metastasis OS samples. To understand the DUSP1 role in the pathogenesis of OS, we assessed the function of DUSP1 in four OS cell lines through a series of cellular assays combined with gene silencing technique. Our findings showed increased MAP2K6, MAP4K3, and DUSP1 gene expression in post-chemotherapy OS samples presenting poor prognosis. We also found that the suppression of DUSP1 gene expression resulted in decreased proliferation, migration, and invasion in OS cells. These results suggest that members of MAPK family may be possible prognostic markers in OS and DUSP1 has a relevant role in the OS pathogenesis and can be an attractive therapeutic target in new strategies of OS treatment.

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Section: Discussionmentioning

confidence: 99%

“…Moreover, upregulation of MAP2K6 have been described in several types of cancer. 34 DUSPs are a family of protein phosphatases, which inactive MAPKs by dephosphorylation of threonine and/or tyrosine residues. DUSP1 plays an essential in the regulation of many cellular responses.…”

Section: Discussionmentioning

confidence: 99%

MAPK pathways regulation by DUSP1 in the development of osteosarcoma: Potential markers and therapeutic targets

Lopes

Tesser-Gamba

Petrilli

et al. 2017

Molecular Carcinogenesis

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“…Such selective probes could be used to investigate the role of MAP2K6 in redox sensing, development, and cancer. 18 EA’s inhibition of MAP2K6, a cellular target unrelated to current uses of EA to treat edema or as a probe for GST function 13 or Wnt signaling, 19 suggests that further studies of EA and related compounds as biological probes might be fruitful. The discovery of this novel ligand interaction site in MAP2K6 through IDUP highlights the potential of unbiased binding assays to reveal probes with unanticipated inhibition mechanisms.…”

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confidence: 99%

Discovery of a Covalent Kinase Inhibitor from a DNA-Encoded Small-Molecule Library × Protein Library Selection

et al. 2017

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We previously reported interaction determination using unpurified proteins (IDUP), a method to selectively amplify DNA sequences encoding ligand:target pairs from a mixture of DNA-linked small molecules and unpurified protein targets in cell lysates. In this study, we applied IDUP to libraries of DNA-encoded bioactive compounds and DNA-tagged human kinases to identify ligand:protein binding partners out of 32 096 possible combinations in a single solution-phase library × library experiment. The results recapitulated known small molecule:protein interactions and also revealed that ethacrynic acid is a novel ligand and inhibitor of MAP2K6 kinase. Ethacrynic acid inhibits MAP2K6 in part through alkylation of a nonconserved cysteine residue. This work validates the ability of IDUP to discover ligands for proteins of biomedical relevance.

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“…In our previous study we have reported a dramatic up-regulation of the MKK6 in esophageal, stomach and colon cancers [7], and as already mentioned an upregulation has also been reported in prostatic carcinomas [5]. The expression pattern of MKK6 has never been systematically evaluated in breast cancer and the specific role of MKK6 in breast cancer progression is incompletely understood.…”

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confidence: 99%

“…In order to significantly augment our understanding of the metastatic process and to identify the specific targets for cancer therapy we need to single out the proteins and signaling pathways necessary for regulation of metastasis. In various cancers many proteins show differential expression and regulation [5][6][7]. One such protein is mitogen-activated protein kinase 6 (which from now onwards will be referred to as MKK6).…”

Section: …………………………………………………………………………………………………… Introduction:-mentioning

confidence: 99%

Involvement of Mitogen-Activated Protein Kinase Kinase 6 in Breast Tumorigenesis.

Baba¹,

Mushtaq²,

Parray³

et al. 2017

IJAR

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MKK6 expression analysis has been reported in various primary tumors, like esophagus, stomach, colon and prostate cancers but its significance in primary breast tumor patients remains unclear. We investigated the expression of MKK6 in cancer tissues through immunoblotting and immunofluorescence techniques in 25 resected cases of human breast carcinomas. Increased MKK6 protein expression was observed in 56% (14 ⁄ 25) of breast cancer cases. These results indicate that the upregulated expression of MKK6 in cancer tissues has significant role in tumor progression and the clinical prognosis of patients with primary breast carcinoma. …………………………………………………………………………………………………….... Introduction:-Breast cancer is one of the most common cancers with more than 1.3 million cases and 0.45 million deaths each year worldwide [1]. It is the number one cancer amongst females accounting for 5.59% of total cancers in females of Kashmir valley only [2]. Breast cancer development involves progression through chain of intermediate processes, which starts with ductal hyper-proliferation, followed by subsequent progression to carcinoma in situ, invasive carcinoma, and finally into metastatic disease [3]. Studies have shown that metastasis is a series of diverse events, generally known as a metastatic cascade. These steps include fleeing of malignant cells from the site of primary tumor, propagation and shifting to a discontinuous secondary site(s), and lastly, the survival and growth into clinically detectable metastases, a process termed metastatic colonization [4]. In order to significantly augment our understanding of the metastatic process and to identify the specific targets for cancer therapy we need to single out the proteins and signaling pathways necessary for regulation of metastasis. In various cancers many proteins show differential expression and regulation [5][6][7]. One such protein is mitogen-activated protein kinase 6 (which from now onwards will be referred to as MKK6). MKK6 belongs to the mitogen-activated protein (MAP) kinase super family and has a role in both apoptosis [8,9] as well as proliferation [10]. MKK6 has been implicated in regulating tumorigenesis. MKK6 has been shown to play contradictory roles in suppressing metastatic colonization in human ovarian carcinoma [11] on other hand it has been shown to be up-regulated in prostate cancers [12]. As of now, very little is known about the regulation of expression of MKK6 in the cell [13]. MKK6 activates downstream all the isoforms of p38 MAPK [14]. P38α has been implicated in regulating cancer progression, by regulating invasion, inflammation and angiogenesis which are key oncogenic steps in tumorogenesis [15][16][17].

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MKK6 is Upregulated in Human Esophageal, Stomach, and Colon Cancers

Cited by 30 publications

References 37 publications

MAPK pathways regulation by DUSP1 in the development of osteosarcoma: Potential markers and therapeutic targets

MAPK pathways regulation by DUSP1 in the development of osteosarcoma: Potential markers and therapeutic targets

Discovery of a Covalent Kinase Inhibitor from a DNA-Encoded Small-Molecule Library × Protein Library Selection

Involvement of Mitogen-Activated Protein Kinase Kinase 6 in Breast Tumorigenesis.

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