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  current news   Press   selected story    
     
  3 June 2015  
 
Congratulations to IMCB’s recent PhD graduate
 
 




Thesis title: A Role of PRL-3 in autophagy and its regulation in human cancers

Abstract
PRL-3 (PTP4A3) is a metastatic phosphatase localizes in plasma membrane and endosomes. It functions to promote multiple oncogenetic processes such as cell proliferation, angiogenesis, invasion and metastasis. Recently, we found the correlation of PRL-3 and autophagy. Autophagy is a “self-eating” process which has dual roles in promoting or suppressing tumor growth, depending on cellular context. In this study, I showed that PRL-3 overexpression enhances hVps34-Beclin-1-dependent autophagosome formation and accelerates LC3-I to LC3-II conversion dependent on ATG5 expression. PRL-3 overexpression also accelerates the degradation of SQSTM/p62, which is a known autophagy substrate. Surprisingly, PRL-3 itself is also degraded by autophagy specifically, forming a negative feedback loop with autophagy. Clinically, PRL-3 is dependent on autophagy activity in promoting ovarian cancer progression. In addition, I also showed that constitutively activated mutation of KRas, which is essential in the development of many human cancers, specifically upregulated PRL-3 protein level. My study showed new mechanisms of PRL-3 regulations as well as the pathways affected by PRL-3, which will give some new clues to targeted cancer therapy for PRL-3 overexpressing tumors.

Figure:


Figure Legend:
A proposed model of coverage between PRL-3, KRas signaling, and autophagy signaling. PRL-3 activates autophagosome formation and is also degraded by autophagy. Constitutively active mutation of KRas stabilizes PRL-3 through the RAF/MEK/ERK kinase cascade. Solid lines indicate direct regulation, while dotted line indicated indirect regulation. Black lines are based on existing literature, and red lines show novel finding in this study.

Publications:
Huang YH*, Al-Aidaroos AQ*, Yuen HF*, Zhang SD, Shen HM, Rozycka E, McCrudden CM, Tergaonkar V, Gupta A, Lin YB, Thiery JP, Murray JT, Zeng Q. A role of autophagy in PTP4A3-driven cancer progression. Autophagy. 2014 Aug 1;10(10).

For more information on Qi ZENG's laboratory please click here.