Alpha-1-syntrophin protein is differentially expressed in human cancers

Bhat, Zuhaib F.; Baba, Rafia A.; Bashir, Muneesa; Saeed, Safder; Kirmani, Deeba; Wani, Mudassir Maqbool; Wani, Nisar Ahmad; Wani, Khursheed Alam; Khanday, Firdous A.

doi:10.3109/1354750x.2010.522731

Cited by 27 publications

(17 citation statements)

References 31 publications

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“…In another such study, SNTA1 was found to be a potential marker of metastases or tumour progression, which could potentially aid in the classification of pre-malignant lesions, in tongue squamous cell carcinomas (SCCs) (Carinci et al , 2005). In addition, in our previous work, we observed an increase in SNTA1 protein levels in human breast carcinoma tissue samples when compared with their respective adjacent controls, suggesting that it has a role in the development and progression of carcinogenesis (Bhat et al , 2010). …”

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confidence: 64%

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Role of SNTA1 in Rac1 activation, modulation of ROS generation, and migratory potential of human breast cancer cells

et al. 2014

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Background:Alpha-1-syntrophin (SNTA1) has been implicated in the activation of Rac1. However, the underlying mechanism has not yet been explored. Here, we show that a novel complex, involving SNTA1, P66shc, and Grb2 proteins, is involved in Rac1 activation.Methods:Co-immunoprecipitation assays were used to show the complex formation, while siRNAs and shRNAs were used to downregulate expression of these proteins. Various Rac1 activation assays and functional assays, such as migration assays, in vitro wound healing assays, cell proliferation assays, and ROS generation assays, were also performed.Results:The results showed a significant increase in activation of Rac1 when SNTA1 and P66shc were overexpressed, whereas depletion of SNTA1 and P66shc expression effectively reduced the levels of active Rac1. The results indicated a significant displacement of Sos1 protein from Grb2 when SNTA1 and P66shc are overexpressed in breast cancer cell lines, resulting in Sos1 predominantly forming a complex with Eps8 and E3b1. In addition, the SNTA1/P66shc-mediated Rac1 activation resulted in an increase in reactive oxygen species (ROS) production and migratory potential in human breast cancer cells.Conclusion:Together, our results present a possible mechanism of Rac1 activation involving SNTA1 and emphasise its role in ROS generation, cell migration, and acquisition of malignancy.

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confidence: 64%

“…SNTA1, P66shc, and Grb2 have been shown to be upregulated in breast carcinomas and have roles in breast cancer development and/or progression (Jackson et al , 2000; Bhat et al , 2010). These proteins have also been implicated in the Rac1 protein activation pathway.…”

Section: Discussionmentioning

confidence: 99%

Role of SNTA1 in Rac1 activation, modulation of ROS generation, and migratory potential of human breast cancer cells

et al. 2014

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“…Genes, which were significantly associated with the pathway networks in IPA were searched in the literature for their roles in breast cancer and are compiled along with relevant references in Table 5 for upregulated genes and in Table 6 for downregulated genes. A total of 27 upregulated (ACHE [11], HSPA1L [12], NES [13], P2RY2 [14], PLCG1 [15], PPARGC1A [16], PRKCQ [17], SNTA1 [18], ALDOA [19], GNAO1 [20], SLC16A3 [21], TPI1 [22], ELL2 [23], CCNG1 [24], E2F6 [25], ESRRG [26], MAPK12 [27], HSD17B7 [28], TACC2 [29], DDX1 [30], MYH1 [31], UCP1 [32], PACSIN3 [33], PGM1 [34], TLN2 [35], ADIPOR1 [36], PITX1 [37]) and 8 downregulated genes (CELSR2 [38], PRKCB [39], KIT [40], MAP2 [41], TDGF1 [42], ELF1 [43], RUNX1 [44], TYMS [45]) showed association with breast cancer. Furthermore, the data files with the complete list of the upregulated and downregulated networks are presented in Additional files 3 and 4, respectively, for further reference.…”

Section: Resultsmentioning

confidence: 99%

Exposure to ionizing radiation induced persistent gene expression changes in mouse mammary gland

et al. 2012

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BackgroundBreast tissue is among the most sensitive tissues to the carcinogenic actions of ionizing radiation and epidemiological studies have linked radiation exposure to breast cancer. Currently, molecular understanding of radiation carcinogenesis in mammary gland is hindered due to the scarcity of in vivo long-term follow up data. We undertook this study to delineate radiation-induced persistent alterations in gene expression in mouse mammary glands 2-month after radiation exposure.MethodsSix to eight week old female C57BL/6J mice were exposed to 2 Gy of whole body γ radiation and mammary glands were surgically removed 2-month after radiation. RNA was isolated and microarray hybridization performed for gene expression analysis. Ingenuity Pathway Analysis (IPA) was used for biological interpretation of microarray data. Real time quantitative PCR was performed on selected genes to confirm the microarray data.ResultsCompared to untreated controls, the mRNA levels of a total of 737 genes were significantly (p<0.05) perturbed above 2-fold of control. More genes (493 genes; 67%) were upregulated than the number of downregulated genes (244 genes; 33%). Functional analysis of the upregulated genes mapped to cell proliferation and cancer related canonical pathways such as ‘ERK/MAPK signaling’, ‘CDK5 signaling’, and ‘14-3-3-mediated signaling’. We also observed upregulation of breast cancer related canonical pathways such as ‘breast cancer regulation by Stathmin1’, and ‘HER-2 signaling in breast cancer’ in IPA. Interestingly, the downregulated genes mapped to fewer canonical pathways involved in cell proliferation. We also observed that a number of genes with tumor suppressor function (GPRC5A, ELF1, NAB2, Sema4D, ACPP, MAP2, RUNX1) persistently remained downregulated in response to radiation exposure. Results from qRT-PCR on five selected differentially expressed genes confirmed microarray data. The PCR data on PPP4c, ELF1, MAPK12, PLCG1, and E2F6 showed similar trend in up and downregulation as has been observed with the microarray.ConclusionsExposure to a clinically relevant radiation dose led to long-term activation of mammary gland genes involved in proliferative and metabolic pathways, which are known to have roles in carcinogenesis. When considered along with downregulation of a number of tumor suppressor genes, our study has implications for breast cancer initiation and progression after therapeutic radiation exposure.

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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: 89%

“…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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Alpha-1-syntrophin protein is differentially expressed in human cancers

Cited by 27 publications

References 31 publications

Role of SNTA1 in Rac1 activation, modulation of ROS generation, and migratory potential of human breast cancer cells

Role of SNTA1 in Rac1 activation, modulation of ROS generation, and migratory potential of human breast cancer cells

Exposure to ionizing radiation induced persistent gene expression changes in mouse mammary gland

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

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