Opposing prognostic roles of nuclear and cytoplasmic RACGAP1 expression in colorectal cancer patients

Yeh, Chung-Min; Sung, Wen‐Wei; Lai, Hung-Wen; Hsieh, Ming‐Ju; Yen, Hsu‐Heng; Su, Tzu-Cheng; Chang, Wen-Hsin; Chen, Chia-Yu; Ko, Jiunn‐Liang; Chen, Chih‐Jung

doi:10.1016/j.humpath.2015.09.002

Cited by 17 publications

(16 citation statements)

References 22 publications

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“…Similarly, patients with positive RacGAP1 protein expression at the invasive front of gastric cancer showed poorer prognosis than those without it . Interestingly, colorectal cancer patients had opposite prognoses depending on the site of RacGAP1 expression, in that patients with high nuclear RacGAP1 expression had poor outcomes, whereas those with high cytoplasmic RacGAP1 expression had favorable prognoses. It is fascinating that different localization of RacGAP1 may drive distinct signaling pathways and opposite effects.…”

Section: Discussionmentioning

confidence: 99%

“…22 Similarly, patients with positive RacGAP1 protein expression at the invasive front of gastric cancer showed poorer prognosis than those without it. 20 Interestingly, colorectal cancer patients had opposite prognoses depending on the site of RacGAP1 expression, 26 in that patients resistance was reported to be mediated by RacGAP1-dependent activation of AKT. Knockdown of RacGAP1 in HNSCC cells showed slower growth and sensitized the cytotoxic actions of doxorubicin in mice models.…”

Section: Discussionmentioning

confidence: 99%

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Rac GTPase activating protein 1 promotes oncogenic progression of epithelial ovarian cancer

Wang

Liu

et al. 2017

Cancer Science

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Rac GTPase activating protein 1 (RacGAP1) can regulate cytokinesis and cell differentiation. The oncogenic role of RacGAP1 has been partially studied in gastric cancer, colorectal cancer, and breast cancer. In the present study, we endeavor to evaluate its expression and functions in epithelial ovarian cancer (EOC). We retrospectively collected the clinicopathological information of 117 patients who underwent curative surgery for EOC. Expression of RacGAP1 protein in primary tumor tissues was evaluated by immunohistochemistry, which was significantly associated with tumor pathological grade, tumor stage, and lymph node metastasis. Patients with lower RacGAP1 level had a longer survival time and lower recurrence risk. Multivariate results identified the independent prognostic role of RacGAP1 for both recurrence and survival in EOC patients. Cellular studies showed that RacGAP1 can positively regulate the activation of RhoA and Erk proteins. In addition, wound healing assay and Transwell assay found that RacGAP1 can up‐regulate the migration and invasion process of EOC cells, respectively. In all, our results not only confirmed the prognostic role of RacGAP1 for recurrence and survival in EOC patients, but also highlighted its possible potency for drug development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Rac GTPase activating protein 1 promotes oncogenic progression of epithelial ovarian cancer

Wang

Liu

et al. 2017

Cancer Science

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“…24 Similarly, RACGAP1 overexpression has been reported in several cancers, including breast, colorectal, squamous cell, gastric, uterine, and hepatocellular, and has been linked to increased recurrence and poor prognosis. [42][43][44][45][46][47][48][49] Hence, it appears that pro-tumorigenic ARH-GAP11A and RACGAP1 functions might be conserved between cancer types. Future work should aim to clarify the mechanisms that control the activity of these GAPs in cancer, particularly for ARHGAP11A, of which little is known regarding its regulation.…”

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confidence: 99%

“…50 Interestingly, a recent study suggested that colorectal cancer patients had a worse prognosis when RACGAP1 was highly expressed in the nucleus compared to the cytoplasm. 49 The ability of ARHGAP11A to regulate the cell cycle is presumably linked to its nuclear localization, and future studies should aim to identify ARHGAP11A binding partners so that the exact mechanism of cell cycle control can be determined.…”

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confidence: 99%

Filling GAPs in our knowledge: ARHGAP11A and RACGAP1 act as oncogenes in basal-like breast cancers

Lawson

Der

2016

Small GTPases

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Like RAS proteins, the aberrant function of RHO family small GTPases has been implicated in driving cancer development and growth. However, unlike the RAS family, where gain-of-function missense mutations are found in ∼25% of all human cancers, missense mutations are relatively rare in RHO proteins. Instead, altered RHO activity in cancer more commonly arises through the aberrant functions of RHO GTPase regulators. In many cancer types, altered expression and/or mutation of RHO-selective guanine nucleotide exchange factors (RHOGEFs) or GTPase-activating proteins (RHOGAPs), which activate or inactivate RHO GTPases, respectively, is observed. For example, deletion or loss of expression of the RHOA GAP DLC1 is well-established to drive cancer growth. Recently, we identified high expression of 2 RHOGAPs, ARHGAP11A and RACGAP1, in the basal-like breast cancer subtype. Unexpectedly, both of these RHOA GAPs exhibited properties of oncoproteins rather than tumor suppressors, in contrast to DLC1. In this commentary, we summarize our findings and speculate that different RHOA GAPs can play distinct roles in cancer depending on their spatial regulation and cancer type context. We also evaluate our results in light of recently-described cancer genome sequencing studies that have identified loss-of-function mutations of RHOA in specific cancer types.

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“…RACGAP1 has been correlated with poor outcomes in various tumor types, including breast cancer, hepatocellular carcinoma, gastric cancer, colorectal cancer, epithelial ovarian cancer, esophageal carcinoma, and invasive cervical cancer [43][44][45][46][47][48]. Interestingly, RACGAP1 was reported to be a target gene of mutant p53 [49,50].…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Hub Genes Through Expression Profiles Analysis in Adrenocortical Carcinoma

Yao¹,

Zhao²,

Shang³

et al. 2020

Preprint

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Abstract Background: Adrenocortical carcinoma (ACC) is a heterogeneous and rare malignant tumor associated with a poor prognosis. The molecular mechanisms of ACC remain elusive and more accurate biomarkers for the prediction of prognosis are needed.Methods: In this study, integrative profiling analyses were performed to identify novel hub genes in ACC to provide promising targets for future investigation. Three gene expression profiling datasets in the GEO database were used for the identification of overlapped differentially expressed genes (DEGs) following the criteria of adj.P.Value<0.05 and |log2 FC|>0.5 in ACC. Novel hub genes were screened out following a series of processes: the retrieval of DEGs with no known associations with ACC on Pubmed, then the cross-validation of expression values and significant associations with overall survival in the GEPIA2 and starBase databases, and finally the prediction of gene-tumor association in the GeneCards database.Results: Four novel hub genes were identified and two of them, TPX2 and RACGAP1, were positively correlated with the staging. Interestingly, co-expression analysis revealed that the association between TPX2 and RACGAP1 was the strongest and that the expression of HOXA5 was almost completely independent of that of RACGAP1 and TPX2. Furthermore, the PPI network consisting of four novel genes and seed genes in ACC revealed that HOXA5, TPX2, and RACGAP1 were all associated with TP53. Conclusions: This study identified four novel hub genes (TPX2, RACHAP1, HXOA5 and FMO2) that may play crucial roles in the tumorigenesis and the prediction of prognosis of ACC.

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Opposing prognostic roles of nuclear and cytoplasmic RACGAP1 expression in colorectal cancer patients

Cited by 17 publications

References 22 publications

Rac GTPase activating protein 1 promotes oncogenic progression of epithelial ovarian cancer

Rac GTPase activating protein 1 promotes oncogenic progression of epithelial ovarian cancer

Filling GAPs in our knowledge: ARHGAP11A and RACGAP1 act as oncogenes in basal-like breast cancers

Identification of Novel Hub Genes Through Expression Profiles Analysis in Adrenocortical Carcinoma

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