Differential Regulation of Adhesion Complex Turnover by ROCK1 and ROCK2

Lock, Frances E.; Ryan, Katie R.; Poulter, Natalie S.; Parsons, Maddy; Hotchin, Neil A.

doi:10.1371/journal.pone.0031423

Cited by 73 publications

(61 citation statements)

References 44 publications

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“…Forty micrograms of protein/sample were separated using 4-12% Bis-Tris gels and CAPS transfer buffer (Invitrogen). Western blotting was carried out as described (76). For isoelectric focusing, cells were lysed in RIPA buffer and 500 μg protein processed using ReadyPrep 2D cleanup kit (Bio-Rad).…”

Section: Methodsmentioning

confidence: 99%

Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma

Lock

Rebollo

Miceli-Royer

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Sequences derived from transposable elements (TEs) are abundant in the human genome and can influence gene expression. In normal cells, most TEs are silenced by epigenetic mechanisms such as DNA methylation but, in cancer, normally dormant TEs can become active. We hypothesized that cancer-specific release of epigenetic suppression of TEs could result in gene expression perturbations, which could promote oncogenesis. Using a bioinformatics method, we identified many genes expressed in diffuse large B-cell lymphoma (DLBCL) via activation of TE promoters. Further analysis of one, FABP7 , showed it was expressed in some DLBCL samples through use of a TE promoter. The TE-driven FABP7 transcript encodes a novel isoform of the protein, which is required for optimal DLBCL cell line proliferation.

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Section: Methodsmentioning

confidence: 99%

Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma

Lock

Rebollo

Miceli-Royer

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…AKT activation correlates with enhanced tumor invasion [14,15], and based on the presented results dual ROCK/EGFR treatment antagonizes AKT signaling; which similarly leads to the robust suppression of MAPK/ERK pathway activity. It must be noted, however, that while the ROCK1 and ROCK2 proteins share significant sequence homology, they have been described to exert different functions in the cell [22,23]. ROCK1 is reported to be involved in actin cytoskeleton destabilization while ROCK2 has been shown to be an essential factor in stabilizing the actin cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

Combined inhibition of rho-associated protein kinase and EGFR suppresses the invasive phenotype in EGFR-dependent lung cancer cells

et al. 2015

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a b s t r a c tIntroduction: Lung cancer remains the leading cause of cancer-related mortality worldwide, with metastatic disease frequently a prominent feature at the time of diagnosis. The role of NSCLC-derived EGFR mutations in cancer cell proliferation and survival has been widely reported, but little is known about the function of these mutations in invasive growth and metastasis. In this study, we sought to evaluate the intrinsic invasive properties of NSCLC cells with differing EGFR status and examine possible therapeutic targets that can abrogate invasive growth. Materials and methods: Collagen-based assays and 3D cell cultures were used to assess morphological features, actin cytoskeleton dynamics and the invasive capacity of NSCLC cell lines with differing EGFR status. The role of the RhoA/ROCK/MYPT1 and EGFR/HER pathways in NSCLC-related invasion was investigated by pharmacological inhibition and RNA interference techniques. Results: We demonstrate a positive correlation between EGFR mutational/amplification status and invasive capacity. Knockdown of wild-type and mutant EGFR leads to depletion of active and total MYPT1 levels. Combined pharmacological inhibition or genetic ablation of ROCK/EGFR suppresses the hallmarks of cancer cells and abrogates the invasive phenotype in EGFR-dependent NSCLC cells. Conclusions: These observations suggest that combined targeting of the ROCK and EGFR/HER pathways may be a potential therapeutic approach in limiting invasive growth in NSCLC.

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“…Mammals have two ROCK isoforms, ROCK1 and ROCK2, which have distinct roles in signaling and morphology (Lock et al, 2012). To determine whether the Y-27632 induced multiple lumen phenotype could be attributed to a specific ROCK isoform, we used short hairpin RNA (shRNA) to specifically knockdown (KD) ROCK1 or ROCK2.…”

Section: Rock Inhibition Reduces Cell Movementmentioning

confidence: 99%

P114RhoGEF governs cell motility and lumen formation during tubulogenesis via ROCK-myosin II pathway

Kim

Shewan

Ewald

et al. 2015

Journal of Cell Science

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Tubulogenesis is fundamental to the development of many epithelial organs. Although lumen formation in cysts has received considerable attention, less is known about lumenogenesis in tubes. Here, we utilized tubulogenesis induced by hepatocyte growth factor (HGF) in MDCK cells, which form tubes enclosing a single lumen. We report the mechanism that controls tubular lumenogenesis and limits each tube to a single lumen. Knockdown of p114RhoGEF (also known as ARHGEF18), a guanine nucleotide exchange factor for RhoA, did not perturb the early stages of tubulogenesis induced by HGF. However, this knockdown impaired later stages of tubulogenesis, resulting in multiple lumens in a tube. Inhibition of Rho kinase (ROCK) or myosin IIA, which are downstream of RhoA, led to formation of multiple lumens. We studied lumen formation by live-cell imaging, which revealed that inhibition of this pathway blocked cell movement, suggesting that cell movement is necessary for consolidating multiple lumens into a single lumen. Lumen formation in tubules is mechanistically quite different from lumenogenesis in cysts. Thus, we demonstrate a new pathway that regulates directed cell migration and formation of a single lumen during epithelial tube morphogenesis.

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Differential Regulation of Adhesion Complex Turnover by ROCK1 and ROCK2

Cited by 73 publications

References 44 publications

Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma

Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma

Combined inhibition of rho-associated protein kinase and EGFR suppresses the invasive phenotype in EGFR-dependent lung cancer cells

P114RhoGEF governs cell motility and lumen formation during tubulogenesis via ROCK-myosin II pathway

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