Colon cancer bears overexpression of OTUB1

Liu, Xin; Jiang, Weina; Wang, Jigang; Chen, Hua

doi:10.1016/j.prp.2014.05.008

Cited by 35 publications

(39 citation statements)

References 10 publications

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“…A relatively new oncogene, conflicting roles of OTUB1 have been described in colon cancer and lung tumor cell lines [22, 34]. Our results indicate that OTUB1 exerts oncogenic activities in ovarian cancer and its expression is tightly correlated with FOXM1 in human ovarian cancer samples.…”

Section: Discussionmentioning

confidence: 59%

OTUB1-catalyzed deubiquitination of FOXM1 facilitates tumor progression and predicts a poor prognosis in ovarian cancer

Wang

Zhou

et al. 2016

Oncotarget

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Ubiquitination is essential for regulation of cell physiology, protein stability, and signal transduction [1]. Its dysregulation is an important factor in many diseases, including cancer. We explored the potential OTUB1-catalyzed deubiquitination of FOXM1, a transcription factor linked to carcinogenesis, and the biological consequence of that interaction in ovarian cancer. We found that FOXM1 is ubiquitinated by multiple polyUb chains and targeted for proteosomal degradation in a reaction dependent on its ubiquitination-required KEN box. Additionally, the OTUB1 N-terminus and catalytic triad bind to FOXM1, specifically catalyzing cleavage of the K48-specific ubiquitin linkage from FOXM1. Moreover, OTUB1-FOXM1 interaction drives tumor progression and OTUB1 expression predicts a poor prognosis in ovarian cancer. Our study suggests that inhibiting OTUB1-FOXM1 interaction is a potential new avenue for ovarian cancer therapy.

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Section: Discussionmentioning

confidence: 59%

OTUB1-catalyzed deubiquitination of FOXM1 facilitates tumor progression and predicts a poor prognosis in ovarian cancer

Wang

Zhou

et al. 2016

Oncotarget

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“…Whereas down‐regulation or loss of function of RABEX5 in human cancers has not been reported, we found that OTUB1 expression is commonly up‐regulated in a substantial subset of NSCLCs harboring wt KRAS. Recent studies also report increased expression of OTUB1 in prostate, colorectal, and breast cancers that are associated with poor survival, high metastatic potential, and chemotherapeutic drug resistance (Liu et al , ; Zhou et al , ; Iglesias‐Gato et al , ; Karunarathna et al , ). Importantly, TCGA data analysis revealed that, similarly to lung adenocarcinomas, OTUB1 overexpression in colorectal cancer is mutually exclusive with KRAS mutations (co‐occurrence log odds ratio: −3; P ‐value: 0.003), whereas RAS genes are rarely mutated in prostate and breast cancers (Karnoub & Weinberg, ).…”

Section: Discussionmentioning

confidence: 99%

OTUB 1 triggers lung cancer development by inhibiting RAS monoubiquitination

et al. 2016

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Activation of the RAS oncogenic pathway, frequently ensuing from mutations in RAS genes, is a common event in human cancer. Recent reports demonstrate that reversible ubiquitination of RAS GTPases dramatically affects their activity, suggesting that enzymes involved in regulating RAS ubiquitination may contribute to malignant transformation. Here, we identified the de-ubiquitinase OTUB1 as a negative regulator of RAS mono-and di-ubiquitination. OTUB1 inhibits RAS ubiquitination independently of its catalytic activity resulting in sequestration of RAS on the plasma membrane. OTUB1 promotes RAS activation and tumorigenesis in wild-type RAS cells. An increase of OTUB1 expression is commonly observed in non-small-cell lung carcinomas harboring wild-type KRAS and is associated with increased levels of ERK1/2 phosphorylation, high Ki67 score, and poorer patient survival. Our results strongly indicate that dysregulation of RAS ubiquitination represents an alternative mechanism of RAS activation during lung cancer development.

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“…OTUB1 is abnormally up‐regulated in somatic malignancies and exerts oncogenic functions 26, 32, 33, 34. We have also previously demonstrated that OTUB1 prompted tumour growth and metastasis in ovarian cancer and gastric carcinoma 25, 29.…”

Section: Discussionmentioning

confidence: 80%

The non‐coding RNA OTUB1‐isoform2 promotes ovarian tumour progression and predicts poor prognosis

Wang

Ning

Wei

et al. 2018

J Cellular Molecular Medi

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Ovarian cancer is the leading malignancy of the female reproductive system and is associated with inconspicuous early invasion and metastasis. We have previously reported that the oncogene OTUB1 plays a crucial role in ovarian cancer progression, but the role of its isoform, the non‐coding RNA OTUB1‐isoform2, in ovarian cancer is still elusive. Here, we reported that OTUB1‐isoform2 expression in ovarian cancer tissues was significantly higher than that in the paired paratumorous tissues (P < .01). The patients with high expression of OTUB1‐isoform2 had larger tumours than those with low expression (P < .05). The high expression of OTUB1‐isoform2 was correlated with the involvement of bilateral ovaries (P < .05), lymph node metastasis (P < .05), vascular invasion (P < .05), greater omentum involvement (P < .01), fallopian tube involvement (P < .05), advanced FIGO stages (P < .01) and recurrence (P < .01). Moreover, OTUB1‐isoform2 served as an independent negative prognostic predictor for disease‐free survival (DFS) and disease‐specific survival (DSS). Overexpression of OTUB1‐isoform2 in the ovarian cancer cells stimulated cell proliferation, migration and invasion both in vitro and in vivo. In summary, our study suggested that OTUB1‐isoform2 is a novel prognostic biomarker with independent oncogenic functions for ovarian cancer.

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Colon cancer bears overexpression of OTUB1

Cited by 35 publications

References 10 publications

OTUB1-catalyzed deubiquitination of FOXM1 facilitates tumor progression and predicts a poor prognosis in ovarian cancer

OTUB1-catalyzed deubiquitination of FOXM1 facilitates tumor progression and predicts a poor prognosis in ovarian cancer

OTUB 1 triggers lung cancer development by inhibiting RAS monoubiquitination

The non‐coding RNA OTUB1‐isoform2 promotes ovarian tumour progression and predicts poor prognosis

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