Phosphatase of regenerating liver-3 is regulated by signal transducer and activator of transcription 3 in acute myeloid leukemia

Zhou, Jianbiao; Chong, Phyllis S.Y.; Lu, Xiao; Cheong, Lip-Lee; Bi, Chonglei; Liu, Shaw-Cheng; Zhou, Ya‐Feng; Tan, Tuan Zea; Yang, Henry; Chung, Tae-Hoon; Zeng, Qi; Chng, Wee‐Joo

doi:10.1016/j.exphem.2014.08.001

Cited by 22 publications

(29 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present and previous studies have shown PRL-3 to be transcriptionally regulated by some proteins, including STAT3, p53, and Snail (39)(40)(41). However, regulation of PRL-3 protein stability and turnover remains unknown.…”

Section: Discussionmentioning

confidence: 65%

Ubiquitin-Specific Protease 4-Mediated Deubiquitination and Stabilization of PRL-3 Is Required for Potentiating Colorectal Oncogenesis

Xing

Guo

et al. 2016

Cancer Research

View full text Add to dashboard Cite

Ubiquitin specific protease 4 (USP4) is a deubiquitinating enzyme with key roles in the regulation of p53 and TGFb signaling, suggesting its importance in tumorigenesis. However, the mechanisms and regulatory roles of USP4 in cancer, including colorectal cancer, remain largely elusive. Here, we present the first evidence that USP4 regulates the growth, invasion, and metastasis of colorectal cancer. USP4 expression was significantly elevated in colorectal cancer tissues and was significantly associated with tumor size, differentiation, distant metastasis, and poor survival. Knockdown of USP4 diminished colorectal cancer cell growth, colony formation, migration, and invasion in vitro and metastasis in vivo. Importantly, we found that phosphatase of regenerating liver-3 (PRL-3) is indispensable for USP4-mediated oncogenic activity in colorectal cancer.Mechanistically, we observed that USP4 interacted with and stabilized PRL-3 via deubiquitination. This resulted in activation of Akt and reduction of E-cadherin, critical regulators of cancer cell growth and metastasis. Examination of clinical samples confirmed that USP4 expression positively correlates with PRL-3 protein expression, but not mRNA transcript levels. Taken together, our results demonstrate that aberrant expression of USP4 contributes to the development and progression of colorectal cancer and reveal a critical mechanism underlying USP4-mediated oncogenic activity. These observations suggest that the potential of harnessing proteolytic degradation processes for therapeutic manipulation may offer a much-needed new approach for improving colorectal cancer treatment strategies. Cancer Res; 76(1); 83-95. Ó2015 AACR.

show abstract

Section: Discussionmentioning

confidence: 65%

Ubiquitin-Specific Protease 4-Mediated Deubiquitination and Stabilization of PRL-3 Is Required for Potentiating Colorectal Oncogenesis

Xing

Guo

et al. 2016

Cancer Research

View full text Add to dashboard Cite

show abstract

“…Most recently, it was reported that the signal transducer activator of transcription 3 (STAT3) [23] positively regulates PRL-3 transcription and expression in leukemia cells. Previous reports also showed that the PRL-3 protein contributes to STAT3 activation [13,28,29], suggesting again that PRL-3, as described above for Snail, could participate in a positive autoregulatory feedback loop.…”

Section: Prl-3 Transcriptional Regulatorsmentioning

confidence: 99%

“…Gene amplification is a mechanism to enhance gene expression of oncogenes and could explain PRL-3 overexpression in some human cancer types [4]. Nevertheless, exon sequencing of 10 samples from AML with high levels of PRL-3 did show neither gene amplification nor somatic mutations in PRL-3 [23], suggesting that transcriptional, translational, or posttranslational regulation might be involved in the aberrant expression of PRL-3.…”

Section: Introductionmentioning

confidence: 99%

Regulatory mechanisms of phosphatase of regenerating liver (PRL)-3

Rubio

Köhn

2016

Biochemical Society Transactions

View full text Add to dashboard Cite

The phosphatase of regenerating liver (PRL)-3 is overexpressed in many human cancer types and tumor metastases when compared with healthy tissues. Different pathways and mechanisms have been suggested to modulate PRL-3 expression levels and activity, giving some valuable insights but still leaving an incomplete picture. Investigating these mechanisms could provide new targets for therapeutic drug development. Here, we present an updated overview and summarize recent findings concerning the different PRL-3 expression regulatory mechanisms and posttranslational modifications suggested to modulate the activity, localization, or stability of this phosphatase.

show abstract

“…We have previously shown that PRL-3 is deregulated in myeloid malignancies by STAT activation by upstream oncogenic kinases, such as FLT3 (e.g., in FLT3-ITD AML; refs. 13,21,47). Our results therefore provide potential mechanistic insights to the high relapse rates and poor outcome of FLT3-ITD AML.…”

Section: Discussionmentioning

confidence: 63%

LIN28B Activation by PRL-3 Promotes Leukemogenesis and a Stem Cell–like Transcriptional Program in AML

Zhou

Chan

et al. 2017

Molecular Cancer Research

Self Cite

View full text Add to dashboard Cite

PRL-3 (PTP4A3), a metastasis-associated phosphatase, is also upregulated in patients with acute myeloid leukemia (AML) and is associated with poor prognosis, but the underlying molecular mechanism is unknown. Here, constitutive expression of PRL-3 in human AML cells sustains leukemogenesis in vitro and in vivo. Furthermore, PRL-3 phosphatase activity dependently upregulates LIN28B, a stem cell reprogramming factor, which in turn represses the let-7 mRNA family, inducing a stem cell-like transcriptional program. Notably, elevated levels of LIN28B protein independently associate with worse survival in AML patients. Thus, these results establish a novel signaling axis involving PRL-3/LIN28B/let-7, which confers stem cell-like properties to leukemia cells that is important for leukemogenesis. Implications:The current study offers a rationale for targeting PRL-3 as a therapeutic approach for a subset of AML patients with poor prognosis. Mol Cancer Res; 15(3); 294-303. Ó2016 AACR.

show abstract

Phosphatase of regenerating liver-3 is regulated by signal transducer and activator of transcription 3 in acute myeloid leukemia

Cited by 22 publications

References 56 publications

Ubiquitin-Specific Protease 4-Mediated Deubiquitination and Stabilization of PRL-3 Is Required for Potentiating Colorectal Oncogenesis

Ubiquitin-Specific Protease 4-Mediated Deubiquitination and Stabilization of PRL-3 Is Required for Potentiating Colorectal Oncogenesis

Regulatory mechanisms of phosphatase of regenerating liver (PRL)-3

LIN28B Activation by PRL-3 Promotes Leukemogenesis and a Stem Cell–like Transcriptional Program in AML

Contact Info

Product

Resources

About