In our study, we intend to investigate the role of ROCK1 in tumorigenesis and progression of LSCC. The data exhibit ROCK1 is highly expressed in human LSCC tissues compared to normal tissues, and high expression of ROCK1 correlates with advanced stage and poor survival prognosis for LSCC patients. Furthermore, the data disclose potential molecular mechanism by which the tumor-promoting effects induced by ROCK1 in LSCC are mediated FAK signalling pathway. Here, all findings indicate the key role of ROCK1 as an oncogenic protein and uncover a novel molecular mechanism underlying the development and progression of LSCC.
Dysfunctional ROCK1 regulation leads to genetic instability, potentially contributing to various malignant epithelial tumors, including non-small-cell lung, prostate, pancreatic, colon, esophageal cacers. Higher ROCK1 expression in NSCLC has worse survival . Prostate cancer with high ROCK1 expression was markedly related to advance tumor stage, high classical and quantitative Gleason grade, positive nodal stage, positive surgical margin, and high preoperative PSA level . ROCK1 activities phosphorylation at T558 to promote the metastasis of breast cancer . ROCK1 stimulates the growth and metastasis of pancreatic cancer (PC) cells in vivo and in vitro and ROCK1 may therefore have potential utility as a diagnostic and treatment target in this PC . Here, in our study ROCK1 is highly expressed in human LSCC tissues in comparation to normal tissues, and high expression of ROCK1 correlates with invasion range, lymph node involvement, TNM stage and poor survival prognosis for LSCC patients.
Recent researches imply that ROCK1 has an essential role in cell migration, invasion, ECM synthesis, stress-fiber assembly, mesenchymal-epithelial transition (EMT) and resistance to chemotherapy drug therapy [19–21]. Same as the previous study, ROCK1 plays a multifunctional role in affecting proliferation, migration and invasion of LSCC. And decreasing ROCK1 expression via siRNA inhibits the ability of progression, proliferation, growth, invasion and migration in vitro, as well as pulmonary metastasis in vivo, meanwhile, increasing ROCK1 expression via plasmid transfection has the opposite experimental results. Thus, ROCK1 promoting LSCC tumorigenesis and progression indicates that ROCK1 is a potential objective in LSCC therapy.
Numerous diverse signalling pathways, including ERK1/2 , MAPK , VEGF , WNT  and FAK  have been reported to promote tumor tumorigenesis and progression. FAK signalling pathway is one of the most crucial ones to promote tumorigenesis and progression of various cancers . In our present study, we find ROCK1 promotes LSCC tumorigenesis and progression via the FAK pathway. Knockdown ROCK1 reduces the phosphorylation of FAK and consequently decreases the ability of progression, proliferation, growth, invasion and migration in LSCC. On the contrary, upregulation ROCK1 increases the phosphorylation of FAK and aggrandizes the ability of progression, proliferation, growth, invasion and migration of LSCC. In the next experiment, TAE226, a FAK inhibitor, is applied to indicate the role in promoting LSCC tumorigenesis and progression induced by ROCK1. All results shows that ROCK1 mediates FAK and FAK induced by ROCK1 serves as an important regulator of tumorigenesis and progression of LSCC. Therefore, targeting the molecules ROCK1 and FAK may be regarded as single or combination therapies. Nonetheless, further preclinical trials and relevant researches should be carried out to examine the effect and safe of drugs.
To sum up, we demonstrate that ROCK1 promotes LSCC tumorigenesis and progression via activation of the FAK pathway. Targeting the molecules ROCK1 and FAK might serve as potential targets for clinical LSCC treatment.