Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway

Cai, Sanjun; Chen, Ruihan; Li, Xiaojuan; Cai, Yi; Ye, Zhiqiang; Li, Shigeng; Li, Jun; Huang, Huaiqiu; Peng, Shubin; Wang, Jun; Tao, Yiran; Huang, Hongxing; Wen, Xinglai; Mo, Jianfeng; Deng, Zhupeng; Wang, Jian; Zhang, Yangfan; Gao, Xin; Wen, Xin

doi:10.18632/oncotarget.2880

Cited by 68 publications

(53 citation statements)

References 42 publications

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“…LIMK1 is overexpressed in a variety of malignancies including prostate, gastric, and lung cancers, and significantly promotes tumor cell invasion and metastasis323334. Destrin is also expressed in all colon cancer cell lines examined, and involved in the colon cancer cell migration and invasion35.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of LIMK1–ADF/cofilin by DADS inhibits the migration and invasion of colon cancer

Zhou

Pan

et al. 2017

Sci Rep

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This study aimed to explore whether the downregulation of LIM kinase 1 (LIMK1)-actin depolymerization factor (ADF, also known as destrin)/cofilin by diallyl disulfide (DADS) inhibited the migration and invasion of colon cancer. Previous studies have shown that silencing LIMK1 could significantly enhance the inhibitory effect of DADS on colon cancer cell migration and invasion, suggesting that LIMK1 was a target molecule of DADS, which needed further confirmation. This study reported that LIMK1 and destrin were highly expressed in colon cancer and associated with poor prognosis of patients with colon cancer. Also, the expression of LIMK1 was positively correlated with the expression of destrin. The overexpression of LIMK1 significantly promoted colon cancer cell migration and invasion. DADS obviously inhibited migration and invasion by suppressing the phosphorylation of ADF/cofilin via downregulation of LIMK1 in colon cancer cells. Furthermore, DADS-induced suppression of cell proliferation was enhanced and antagonized by the knockdown and overexpression of LIMK1 in vitro and in vivo, respectively. Similar results were observed for DADS-induced changes in the expression of vimentin, CD34, Ki-67, and E-cadherin in xenografted tumors. These results indicated that LIMK1 was a potential target molecule for the inhibitory effect of DADS on colon cancer cell migration and invasion.

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Section: Discussionmentioning

confidence: 99%

Downregulation of LIMK1–ADF/cofilin by DADS inhibits the migration and invasion of colon cancer

Zhou

Pan

et al. 2017

Sci Rep

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“…Luciferase reporter assays were performed as described previously [30]. Briefly, the putative miR-101 binding sequence of ROCK2 and a mutated sequence of the 3′-UTR of ROCK2 were cloned and named Wt ROCK2 3′UTR and Mut ROCK2 3′UTR.…”

Section: Methodsmentioning

confidence: 99%

Downregulation of miR-101 contributes to epithelial-mesenchymal transition in cisplatin resistance of NSCLC cells by targeting ROCK2

Yin

et al. 2016

Oncotarget

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Chemoresistance and epithelial-mesenchymal transition (EMT) in cancer are linked phenomena. EMT contributes to chemoresistance, however, little is known about whether chemotherapy can induce EMT in cancer cells. Here, we found that miR-101 expression was downregulated in cisplatin-resistant non-small cell lung cancer (NSCLC) cells. Restoration of miR-101 expression inhibited EMT and increased the sensitivity of cisplatin-resistant NSCLC cells to cisplatin in vitro by targeting ROCK2. Furthermore, ROCK2 protein level was inversely correlated with miR-101 level in NSCLC tissue samples. Kaplan-Meier analysis revealed that low miR-101 expression in NSCLC was correlated with poor survival time. In summary, our results provide novel mechanistic insights into the role of miR-101/ROCK2 signaling in the cisplatin resistance of NSCLC cells. Targeting of miR-101 is a potential therapeutic approach for NSCLC.

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“…PAK6 may also be involved in stress-signaling as it is stimulated by p38-MAP kinase (Kaur et al, 2005). Expression of PAK6 is targeted by miR-328 and miR-23a in prostate cancer cells (Liu et al, 2015; Cai et al, 2015), and by miR-429 in colon cancer cells (Tian et al, 2015). PAK6 interacts with the cell junction protein IQGAP1 in a kinase activity-dependent manner and regulates the dissociation of cell-cell junctions in growth factor-stimulated cells (Fram et al, 2014; Morse et al, 2016).…”

Section: Pak6 Biologymentioning

confidence: 99%

“…PAK6 interacts with the cell junction protein IQGAP1 in a kinase activity-dependent manner and regulates the dissociation of cell-cell junctions in growth factor-stimulated cells (Fram et al, 2014; Morse et al, 2016). PAK6 phosphorylates AR (Ser578 (Liu et al, 2013a), Ser308, Ser346, Ser360, Thr326 and Thr354 (Liu et al, 2013b), MDM2 (Thr158 and Ser186) (Liu et al, 2013a), and LIMK1 (Thr508) (Cai et al, 2015) in prostate cancer cells and is involved in cell growth and migration. PAK6 phosphorylates androgen receptor on Ser-578 and marks its degradation via E3 ligase-Mdm2 pathway (Liu et al, 2013).…”

Section: Pak6 Biologymentioning

confidence: 99%

Structure, biochemistry, and biology of PAK kinases

Kumar

Sanawar

et al. 2017

Gene

179

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PAKs, p21-activated kinases, play central roles and act as converging junctions for discrete signals elicited on the cell surface and for a number of intracellular signaling cascades. PAKs phosphorylate a vast number of substrates and act by remodeling cytoskeleton, employing scaffolding, and relocating to distinct subcellular compartments. PAKs affect wide range of processes that are crucial to the cell from regulation of cell motility, survival, redox, metabolism, cell cycle, proliferation, transformation, stress, inflammation, to gene expression. Understandably, their dysregulation disrupts cellular homeostasis and severely impacts key cell functions, and many of those are implicated in a number of human diseases including cancers, neurological disorders, and cardiac disorders. Here we provide an overview of the members of the PAK family and their current status. We give special emphasis to PAK1 and PAK4, the prototypes of groups I and II, for their profound roles in cancer, the nervous system, and the heart. We also highlight other family members. We provide our perspective on the current advancements, their growing importance as strategic therapeutic targets, and our vision on the future of PAKs.

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Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway

Cited by 68 publications

References 42 publications

Downregulation of LIMK1–ADF/cofilin by DADS inhibits the migration and invasion of colon cancer

Downregulation of LIMK1–ADF/cofilin by DADS inhibits the migration and invasion of colon cancer

Downregulation of miR-101 contributes to epithelial-mesenchymal transition in cisplatin resistance of NSCLC cells by targeting ROCK2

Structure, biochemistry, and biology of PAK kinases

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