Immunoexpression of ROCK-1 and MMP-9 as prognostic markers in breast cancer

Bottino, Jenifer; Gelaleti, Gabriela Bottaro; Maschio, Larissa Bazela; Jardim‐Perassi, Bruna V.; Zuccari, Débora Aparecida Pires de Campos

doi:10.1016/j.acthis.2014.08.009

Cited by 33 publications

(36 citation statements)

References 29 publications

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“…A similar observation has been reported for ROCK1 in breast cancer, with a high expression of ROCK1 in metastatic breast tumors compared with nonmetastatic tumors (Liu et al, 2009b) and a correlation with clinicopathologic parameters and overall patient survival (Lane et al, 2008;Bottino et al, 2014).…”

Section: Cancersupporting

confidence: 54%

Rho Kinases in Health and Disease: From Basic Science to Translational Research

Loirand¹

2015

Pharmacol Rev

161

133

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Section: Cancersupporting

confidence: 54%

Rho Kinases in Health and Disease: From Basic Science to Translational Research

Loirand¹

2015

Pharmacol Rev

161

133

View full text Add to dashboard Cite

“…ROCK and RhoA are within a signaling pathway that is often misregulated in breast cancer progression [9–16]. Thus, we examined the expression of ROCK and RhoA in nonmalignant S1 cells and their counterpart malignant T4-2 cells using monolayer plastic (2D) culture and 3D lrECM gel culture.…”

Section: Resultsmentioning

confidence: 99%

“…These alterations eventually enable cancer cells to spread into distant organs and metastasize [8]. mRNA and protein expression of ROCK1, ROCK2 and RhoA are increased in the tissue of breast cancer patients; however, only the increased levels of ROCK1 and RhoA correlate with poor patient prognosis [9–13]. Overexpression of RhoA induces pre-neoplastic transformation in mammary epithelial cells [14].…”

Section: Introductionmentioning

confidence: 99%

Inhibitors of Rho kinase (ROCK) signaling revert the malignant phenotype of breast cancer cells in 3D context

Matsubara

Bissell

2016

Oncotarget

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Loss of polarity and quiescence along with increased cellular invasiveness are associated with breast tumor progression. ROCK plays a central role in actin-cytoskeletal rearrangement. We used physiologically relevant 3D cultures of nonmalignant and cancer cells in gels made of laminin-rich extracellular matrix, to investigate ROCK function. Whereas expression levels of ROCK1 and ROCK2 were elevated in cancer cells compared to nonmalignant cells, this was not observed in 2D cultures. Malignant cells showed increased phosphorylation of MLC, corresponding to disorganized F-actin. Inhibition of ROCK signaling restored polarity, decreased disorganization of F-actin, and led to reduction of proliferation. Inhibition of ROCK also decreased EGFR and Integrinβ1 levels, and consequently suppressed activation of Akt, MAPK and FAK as well as GLUT3 and LDHA levels. Again, ROCK inhibition did not inhibit these molecules in 2D. A triple negative breast cancer cell line, which lacks E-cadherin, had high levels of ROCK but was less sensitive to ROCK inhibitors. Exogenous overexpression of E-cadherin, however, rendered these cells strikingly sensitive to ROCK inhibition. Our results add to the growing literature that demonstrate the importance of context and tissue architecture in determining not only regulation of normal and malignant phenotypes but also drug response.

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“…Also they found variation in the expression of ROCK-1 between different clinical tumor stages, but without a statistically significant difference (p > 0.05). In addition, they found strong labeling areas of ROCK-1 protein in the group of women who had metastases but without a statistically significant difference [47].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Implications of Claudin 4 and Rock 1 in Triple Negative Breast Cancer

Ahmed¹

2017

JCTR

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Abstract:Background: Triple-negative breast cancer (TNBC) is associated with characteristically poor prognosis. Tumor invasion and metastasis lead to high mortality of patients with breast cancer. The identification of biomarkers that allow early detection of metastasis is essential for therapeutic success in the treatment of breast cancer. This study aimed to asses the immune-histochemical expression of Rock-1 and claudin-4 in triple negative breast cancer and comparing them with classic prognostic parameters as age, grade, lymph node state, distant metastasis and stage to evaluate their prognostic significance in triple negative breast cancer. Material and methods: Forty cases of triple negative breast cancer were examined immunohistochemically using antibodies against claudin 4 and ROCK 1. Results: There was a difference in the expression of claudin 4 and Rock 1 among different clinicopathological parameters. A statistically significant relationship was found between high claudin 4 expression and higher age at time of diagnosis, advanced tumor stage, presence of distant metastasis and increased number of nodal involvement (p=0.041, 0.006, 0.001 and < 0.001 respectively). A highly statistically significant relationship was detected between high Rock 1 expression and increased number of nodal involvement (p <0.001). Also the expression of Rock 1 was different according to different age groups, tumor grades, tumor stages and presence or absence of distant metastasis but this difference was statistically insignificant (p=0.388, 0.602, 0.699 and 0. 944 respectively). Conclusion: our data suggest that claudin 4 and ROCK 1 are biomarkers of poor prognosis of patients with triple negative breast cancer.

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Immunoexpression of ROCK-1 and MMP-9 as prognostic markers in breast cancer

Cited by 33 publications

References 29 publications

Rho Kinases in Health and Disease: From Basic Science to Translational Research

Rho Kinases in Health and Disease: From Basic Science to Translational Research

Inhibitors of Rho kinase (ROCK) signaling revert the malignant phenotype of breast cancer cells in 3D context

Prognostic Implications of Claudin 4 and Rock 1 in Triple Negative Breast Cancer

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