Evidence map›Paper›PMID 22942252›Full record

ArticleCancer research2012

ROCK1 and ROCK2 are required for non-small cell lung cancer anchorage-independent growth and invasion.

Dominico Vigil, Tai Young Kim, Ana Plachco, Andrew J Garton, Linda Castaldo, Jonathan A Pachter, Hanqing Dong, Xin Chen, Brianna Tokar, Sharon L Campbell and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

83 citing papers in PubMed, 136 citations in OpenAlex.

  1. Activation of GScience advances · 2026
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23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Dominico VigilLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
Tai Young Kim
Ana Plachco
Andrew J Garton
Linda Castaldo
Jonathan A Pachter
Hanqing Dong
Xin Chen
Brianna Tokar
Sharon L Campbell
Channing J Der
University of North Carolina at Chapel Hill · US

Funding

VALIDATION OF INHIBITORS OF RHO GTPASES FOR CANCER TREATMENTU19CA067771 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI SEBTI, SAID M · 1995 to 2009
$8.9M
Mechanism and role of DLC-1 tumor suppressor loss in lung cancerR01CA129610 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J. · 2008 to 2012
$1.5M
NCI NIH HHS CA129610NCI NIH HHS CA67771NCI NIH HHS R01 CA129610NCI NIH HHS U19 CA067771
6 · The paper itself

Abstract

Evidence is emerging that the closely related ROCK1 and ROCK2 serine/threonine kinases support the invasive and metastatic growth of a spectrum of human cancer types. Therefore, inhibitors of ROCK are under preclinical development. However, a key step in their development involves the identification of genetic biomarkers that will predict ROCK inhibitor antitumor activity. One identified mechanism for ROCK activation in cancer involves the loss of function of the DLC1 tumor suppressor gene, which encodes a GTPase activating protein (RhoGAP) for the RhoA and RhoC small GTPases. DLC-1 loss may lead to hyperactivation of RhoA/C and its downstream effectors, the ROCK kinases. We therefore determined whether loss of DLC-1 protein expression identifies non-small cell lung carcinoma (NSCLC) cell lines whose growth and invasion phenotypes are sensitive to ROCK inhibition. We identified and characterized a novel small molecule pharmacologic inhibitor of ROCK and additionally applied genetic approaches to impair ROCK1 and/or ROCK2 activity, and we determined that although NSCLC anchorage-dependent growth was ROCK-independent, both anchorage-independent growth and Matrigel invasion were ROCK-dependent. However, loss of DLC-1 expression did not correlate with ROCK activation or with OXA-06 sensitivity. Unexpectedly, suppression of ROCK1 or ROCK2 expression alone was sufficient to impair anchorage-independent growth, supporting their nonoverlapping roles in oncogenesis. Mechanistically, the block in anchorage-independent growth was associated with accumulation of cells in the G(0)-G(1) phase of the cell cycle, but not increased anoikis. We conclude that ROCK may be a useful therapeutic target for NSCLC.

Indexed as

Neoplasm InvasivenessActin Depolymerizing FactorsBlotting, WesternCarcinoma, Non-Small-Cell LungCell DivisionCell Line, TumorFlow CytometryHumansLung NeoplasmsPhosphorylationrho-Associated KinasesActin Depolymerizing Factorsrho-Associated KinasesROCK1 protein, humanROCK2 protein, human

Identifiers

PMID22942252
PMCPMC3810962
OpenAlexW2160609627

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.