Immunity to Growth Factor Receptor–Bound Protein 10, a Signal Transduction Molecule, Inhibits the Growth of Breast Cancer in Mice

O-Sullivan, InSug; Chopra, Amla; Carr, Janai R.; Kim, Tae Sung; Cohen, Edward P.

doi:10.1158/0008-5472.can-07-5685

Cited by 14 publications

(9 citation statements)

References 46 publications

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“…LY294002, which was reported to be related to breast cancer cell apoptosis [46], was associated with BRCAT64.1 through the ALACD model ( Fig 4B). Three out of the five genes that were associated with LY294002 and BRCAT64.1 were linked to breast cancer, as supported by the literature [47][48][49]. In addition, BRCAT64.1 was associated with breast cancer in MiTranscriptome with a confidence score larger than 0.5, and was specifically expressed in breast cancer (Fig 4D).…”

Section: The Associations Between Lncrnas and Anti-cancer Drugs In Ansupporting

confidence: 74%

Associating lncRNAs with small molecules via bilevel optimization reveals cancer-related lncRNAs

Wang

Chen

et al. 2019

PLoS Comput Biol

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Long noncoding RNA (lncRNA) transcripts have emerging impacts in cancer studies, which suggests their potential as novel therapeutic agents. However, the molecular mechanism behind their treatment effects is still unclear. Here, we designed a computational model to Associate LncRNAs with Anti-Cancer Drugs (ALACD) based on a bilevel optimization model, which optimized the gene signature overlap in the upper level and imputed the missing lncRNA-gene association in the lower level. ALACD predicts genes coexpressed with lncRNAs mean while matching drug's gene signatures. This model allows us to borrow the target gene information of small molecules to understand the mechanisms of action of lncRNAs and their roles in cancer. The ALACD model was systematically applied to the 10 cancer types in The Cancer Genome Atlas (TCGA) that had matched lncRNA and mRNA expression data. Cancer type-specific lncRNAs and associated drugs were identified. These lncRNAs show significantly different expression levels in cancer patients. Follow-up functional and molecular pathway analysis suggest the gene signatures bridging drugs and lncRNAs are closely related to cancer development. Importantly, patient survival information and evidence from the literature suggest that the lncRNAs and drug-lncRNA associations identified by the ALACD model can provide an alternative choice for cancer targeting treatment and potential cancer pognostic biomarkers. The ALACD model is freely available at https://github.com/wangyc82/ALACD-v1.

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Section: The Associations Between Lncrnas and Anti-cancer Drugs In Ansupporting

confidence: 74%

Associating lncRNAs with small molecules via bilevel optimization reveals cancer-related lncRNAs

Wang

Chen

et al. 2019

PLoS Comput Biol

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“…CSF3 is in PDB, and is related to immune system functions [56]. GRB7 (GRB10) has roles in the immune system and in cancer [57]. HGF is related to plasminogen, which plays critical roles in autoimmune diseases together with matrix metalloproteinase (MMP) 9 [58].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic Screening of Autoimmune Disease Genes and Protein Structure Prediction with FAMS for Drug Discovery

Ishida¹,

Umeyama²,

Iwadate³

et al. 2013

PPL

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Autoimmune diseases are often intractable because their causes are unknown. Identifying which genes contribute to these diseases may allow us to understand the pathogenesis, but it is difficult to determine which genes contribute to disease. Recently, epigenetic information has been considered to activate/deactivate disease-related genes. Thus, it may also be useful to study epigenetic information that differs between healthy controls and patients with autoimmune disease. Among several types of epigenetic information, promoter methylation is believed to be one of the most important factors. Here, we propose that principal component analysis is useful to identify specific gene promoters that are differently methylated between the normal healthy controls and patients with autoimmune disease. Full Automatic Modeling System (FAMS) was used to predict the three-dimensional structures of selected proteins and successfully inferred relatively confident structures. Several possibilities of the application to the drug discovery based on obtained structures are discussed.

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“…Reminiscent of the human form of the disease, Grb14 excess promoted metastasis into the lungs and surrounding structures. Grb7 and 10 have been reported to similarly facilitate tumor formation in ovarian and breast cancer models (Wang et al, 2010,Bai and Luoh, 2008,Sullivan et al, 2008). Moreover, over-expression of Grb14 has been described in clear cell ovarian cancer (Marchini et al, 2008) and RET-mutation associated thyroid tumor xenografts (Engelmann et al, 2009), but the molecular mechanism remains unclear.…”

Section: Discussionmentioning

confidence: 99%

The insulin resistance Grb14 adaptor protein promotes thyroid cancer ret signaling and progression

et al. 2011

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The growth factor receptor-bound protein (Grb) 14 is an adapter molecule of the Grb7/10/14 family with characteristic BPS domains serving to avidly bind tyrosine kinases. Grb14 inhibits insulin receptor (IR) catalytic activity through interaction with the BPS domain and impedes peptide substrate binding. Members of this Grb family have also been shown to interact with other kinases through their SH2 domain. Here we examined the functional role of Grb14 in thyroid cancer using loss- and gain-of-function approaches. Stable knockdown of Grb14 in thyroid cancer cells facilitated insulin receptor signaling. In contrast, RET phosphorylation was diminished in concert with reduced activation of Akt and STAT3. Loss of Grb14 also resulted in diminished cell proliferation and invasion both in vitro and in mouse flank xenografts. In complementary studies, forced expression of Grb14 interrupted insulin receptor signaling but facilitated RET activation, STAT3, and Akt phosphorylation. Consistent with these findings Grb14 over-expression enhanced cell invasion and resulted in striking metastases in an orthotopic thyroid cancer mouse xenograft model. Primary human thyroid cancer microarrays revealed a positive correlation between Grb14 expression and invasive behavior. Our findings uncover a new role for Grb14 in finely tuning receptor signaling and modulating thyroid cancer progression.

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Immunity to Growth Factor Receptor–Bound Protein 10, a Signal Transduction Molecule, Inhibits the Growth of Breast Cancer in Mice

Cited by 14 publications

References 46 publications

Associating lncRNAs with small molecules via bilevel optimization reveals cancer-related lncRNAs

Associating lncRNAs with small molecules via bilevel optimization reveals cancer-related lncRNAs

Bioinformatic Screening of Autoimmune Disease Genes and Protein Structure Prediction with FAMS for Drug Discovery

The insulin resistance Grb14 adaptor protein promotes thyroid cancer ret signaling and progression

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