Coordinate Loss of <i>MAP3K7</i> and <i>CHD1</i> Promotes Aggressive Prostate Cancer

Rodrigues, Lindsey Ulkus; Rider, Leah; Nieto, Cera; Romero, Lina; Karimpour-Fard, Anis; Loda, Massimo; Lucia, M. Scott; Wu, Min; Shi, Lihong; Cimic, Adela; Sirintrapun, S. Joseph; Nolley, Rosalie; Pac, Colton T.; Chen, Haitao; Peehl, Donna M.; Xu, Jianfeng; Liu, Wennuan; Costello, James C.; Cramer, Scott D.

doi:10.1158/0008-5472.can-14-1596

Cited by 79 publications

(112 citation statements)

References 48 publications

(101 reference statements)

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“…SOX2 is by no means unique in this regard. For example, MAP3K7 and CHD1 have been shown to be co-deleted in prostate cancer and their co-deletion in ETS rearrangement-negative prostate cancers correlates with poor patient disease-free survival [61]. In a mouse xenograft model of prostate cancer, knockdown of MAK3K7 on its own had no significant effect on survival and knockdown of CHD1 on its own enhanced survival.…”

Section: Discussionmentioning

confidence: 99%

“…In a mouse xenograft model of prostate cancer, knockdown of MAK3K7 on its own had no significant effect on survival and knockdown of CHD1 on its own enhanced survival. However, combined knockdown of MAK3K7 and CHD1 led to larger tumor volumes and shorter survival [61]. Accordingly, we posit that the identification and targeting of genes that must change in concert with increases in SOX2 could provide a novel strategy for blocking, or at least, reducing the growth of tumors dependent on SOX2.…”

Section: Discussionmentioning

confidence: 99%

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SOX2 functions as a molecular rheostat to control the growth, tumorigenicity and drug responses of pancreatic ductal adenocarcinoma cells

et al. 2016

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Pancreatic ductal adenocarcinoma (PDAC) is a highly deadly malignancy. Expression of the stem cell transcription factor SOX2 increases during progression of PDAC. Knockdown of SOX2 in PDAC cell lines decreases growth in vitro; whereas, stable overexpression of SOX2 in one PDAC cell line reportedly increases growth in vitro. Here, we reexamined the role of SOX2 in PDAC cells, because inducible SOX2 overexpression in other tumor cell types inhibits growth. In this study, four PDAC cell lines were engineered for inducible overexpression of SOX2 or inducible knockdown of SOX2. Remarkably, inducible overexpression of SOX2 in PDAC cells inhibits growth in vitro and reduces tumorigenicity. Additionally, inducible knockdown of SOX2 in PDAC cells reduces growth in vitro and in vivo. Thus, growth and tumorigenicity of PDAC cells is highly dependent on the expression of optimal levels of SOX2 – a hallmark of molecular rheostats. We also determined that SOX2 alters the responses of PDAC cells to drugs used in PDAC clinical trials. Increasing SOX2 reduces growth inhibition mediated by MEK and AKT inhibitors; whereas knockdown of SOX2 further reduces growth when PDAC cells are treated with these inhibitors. Thus, targeting SOX2, or its mode of action, could improve the treatment of PDAC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

SOX2 functions as a molecular rheostat to control the growth, tumorigenicity and drug responses of pancreatic ductal adenocarcinoma cells

et al. 2016

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“…52 However, this tissue also showed the presence of tumor suppressor CHD1. 53 Decreased level β-actin in primary tumor in response to possible cytoskeleton dynamic modification…”

Section: Resultsmentioning

confidence: 99%

Morpho/Proteomic Comparative between High Grade Pleomorphic Sarcoma and Metastasis Diagnosed in an Old Captive Common Hippo

Silva¹,

Lacerda²,

Faria³

et al. 2017

J. Braz. Chem. Soc.

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Old age is a risk factor for cancer development in humans and animals, and studies have shown that tumors in animals are acceptable models for studying human cancers, considering the similarities between their factors. This work was conducted in a 53-year-old captive female common hippo (Hippopotamus amphibious) with a left leg tumor and metastatic mass. Histopathological and immunohistochemical analyses were carried out with a final diagnosis of a high grade pleomorphic sarcoma. A proteomic study using mass spectrometry was added in order to identify further aspects of the primary tumor and metastasis which could improve our understanding, and each tissue showed a proteomic profile indicative of its pathologic state with significant differences between healthy tissue, primary and metastatic tumors. Low levels of β-actin in primary tumors were identified, and this may be associated with a possible consequence of cytoskeleton dynamic modification. In metastatic tissue, these dynamics may be affected by the presence of HSP chaperone 60. Keywords:Hippopotamus amphibious, high grade pleomorphic sarcoma, cytoskeleton, β-actin, mass spectrometry IntroductionOncogenic phenomena in animals include a wide variety of benign and malignant tumors that develop during the life of the animal and have several health consequences. 1 Species with large bodies tend to have a lower cancer rate, which seems to indicate the presence of complex tumor detection systems (Peto's paradox).2 To illustrate this paradox, in contrast with humans, who have only two copies of the TP53 tumor suppressor gene, elephants, the largest of the land mammmals, have 20 copies of the TP53 gene. This allows for extra efficiency in their systems, enabling the correction of DNA damage or inducing apoptosis in mutated cells. As a result, only 3% of elephants develop cancer. 3,4 Despite some comparative cancer and lifespan analyses between wild and zoo animals showing that captive animals were susceptible to cancer and decreased longevity. 5,6 Tidière et al. 7 revealed that mammals from zoo populations generally lived longer than their wild counterparts (84% of species). Of particular interest, the common hippopotamus (Hippopotamus amphibius), a robust mammal with an estimated 40-year lifespan in nature and with slow pace of life, has increased longevity in captivity. [7][8][9] The relationship between life expectancy and environment may be associated with the low caloric diet and reduced metabolism present in captive animals, which slows ageing and the appearance of cancer cases. This is also true for humans. 10,11 Paradoxically, the exceptional longevity these captive animals exhibit can be associated with cancer due to several factors such as telomere shortening, increased cellular senescence, accumulation mutation of DNA in stem and progenitor cells required for active replenishment during the lifespan of the organism, mutations in tumor suppressor genes and metabolic changes. 12-14Based on available database information and proteomics approach, it is poss...

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“…Since hPAF1/PD2 is proposed to have an oncogenic function and is aberrantly overexpressed in pancreatic cancer, and hPAF/PD2 facilitates CHD1 activity, this again suggests that CHD1 plays a pro-oncogenic role. There is some indication that CHD1 functionally interacts with MAP3K7, as co-deletion of CHD1 and MAP3K7 occurs in prostate cancer and co-suppression of Chd1 and Map3k7 in mouse prostate epithelial stem/progenitor cells inhibits differentiation and causes aggressive prostate tumors (Rodrigues et al 2015). CHD1 also works in concert with the androgen receptor (AR), as it is required for AR-dependent transcriptional activation of androgen-responsive genes in prostate cancer (Burkhardt et al 2013).…”

Section: Subfamily I: Chd1 Chd2mentioning

confidence: 99%

The Chromodomain Helicase DNA-Binding Chromatin Remodelers: Family Traits that Protect from and Promote Cancer

Mills

2017

Cold Spring Harb Perspect Med

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A plethora of mutations in chromatin regulators in diverse human cancers is emerging, attesting to the pivotal role of chromatin dynamics in tumorigenesis. A recurrent theme is inactivation of the Chromodomain Helicase DNA-binding (CHD) family of proteins—ATP-dependent chromatin remodelers that govern the cellular machinery’s access to DNA, thereby controlling fundamental processes including transcription, proliferation, and DNA damage repair. This review highlights what is currently known about how genetic and epigenetic perturbation of CHD proteins and the pathways they regulate set the stage for cancer, providing new insight for designing more effective anti-cancer therapies.

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Coordinate Loss of MAP3K7 and CHD1 Promotes Aggressive Prostate Cancer

Cited by 79 publications

References 48 publications

SOX2 functions as a molecular rheostat to control the growth, tumorigenicity and drug responses of pancreatic ductal adenocarcinoma cells

SOX2 functions as a molecular rheostat to control the growth, tumorigenicity and drug responses of pancreatic ductal adenocarcinoma cells

Morpho/Proteomic Comparative between High Grade Pleomorphic Sarcoma and Metastasis Diagnosed in an Old Captive Common Hippo

The Chromodomain Helicase DNA-Binding Chromatin Remodelers: Family Traits that Protect from and Promote Cancer

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