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PAK4 confers the malignance of cervical cancers and contributes to the cisplatin-resistance in cervical cancer cells via PI3K/AKT pathway.

Shu XR, Wu J, Sun H, Chi LQ, Wang JH - Diagn Pathol (2015)

Bottom Line: In addition, the PI3K/Akt pathway has been implicated in the PAK4-confered cisplatin resistance.And the PI3K/Akt inhibitor, LY294002, markedly deteriorated the cisplatin-mediated viability reduction of Hela or Caski cells, indicating the involvement of PI3K/Akt pathway in the cisplatin resistance in cervical cancer cells.This study has confirmed the significant prognostic role of PAK4 level in cervical cancer patients and has recognized the regulatory role in cervical cancer progression.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical Science and Technology, Tianjin University, No. 92, Weijin Road, Nankai District, Tianjin, 300072, China.

ABSTRACT

Background: Multiple protein or microRNA markers have been recognized to contribute to the progression and recurrence of cervical cancers. Particular those, which are associated with the chemo- or radio-resistance of cervical cancers, have been proposed to be promising and to facilitate the definition for cervical cancer treatment options.

Methods: This study was designed to explore the potential prognosis value of p21-activated kinase (PAK)-4 in cervical cancer, via the Kaplan-Meier analysis, log-rank test and Cox regression analysis, and then to investigate the regulatory role of PAK4 in the cisplatin resistance in cervical cancer cells, via the strategies of both PAK4 overexpression and PAK4 knockout.

Results: It was demonstrated that PAK4 was upregulated in cervical cancer tissues, in an association with the cancer's malignance variables such as FIGO stage, lymph node or distant metastasis and the poor histological grade. The high PAK4 expression was also independently associated with poor prognosis to cervical cancer patients. Moreover, PAK4 confers cisplatin resistance in cervical cancer Hela or Caski cells. In addition, the PI3K/Akt pathway has been implicated in the PAK4-confered cisplatin resistance. And the PI3K/Akt inhibitor, LY294002, markedly deteriorated the cisplatin-mediated viability reduction of Hela or Caski cells, indicating the involvement of PI3K/Akt pathway in the cisplatin resistance in cervical cancer cells.

Conclusion: This study has confirmed the significant prognostic role of PAK4 level in cervical cancer patients and has recognized the regulatory role in cervical cancer progression. Moreover, our study has indicated that PAK4 also confers the chemoresistance of cervical cancer cells in a PI3K/Akt-dependent way. Thus, our study indicates PAK4 as a promising marker for cervical cancer treatment.

No MeSH data available.


Related in: MedlinePlus

PAK4 is upregulated in cervical cancer specimens and associates with poor overall survival. a Upregulated PAK4 mRNA level in the intra-tumor specimens than in the peritumor specimens of cervical cancer patients, with paired t test; b Increased PAK4 mRNA level in cervical cancer specimens, with unpaired t test; c Kaplan-Meier survival analysis for high PAK4 expression level (>1) versus low PAK4 expression level (≤1) in patients with cervical cancer. Statistical significance was considered when p < 0.05
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Fig1: PAK4 is upregulated in cervical cancer specimens and associates with poor overall survival. a Upregulated PAK4 mRNA level in the intra-tumor specimens than in the peritumor specimens of cervical cancer patients, with paired t test; b Increased PAK4 mRNA level in cervical cancer specimens, with unpaired t test; c Kaplan-Meier survival analysis for high PAK4 expression level (>1) versus low PAK4 expression level (≤1) in patients with cervical cancer. Statistical significance was considered when p < 0.05

Mentions: There were total of 93 cases of cervical cancer patients were involved in this study. As shown in table 1, these patients were aged from 30 to 75 year, with a median age of 53 years. The detailed tumor clinic-pathological characteristics of all patients, such as tumor size, HPV infection, tumor histology and histological grade, FIGO stage, distant and lymph node metastasis are summarized in table 1. And the PAK4 expression in mRNA level in the peritumor tissue (more than 2 cm from tumor tissue) and in tumor tissue in each patient was examined with RT-qPCR method. Figure 1 demonstrated that the relative PAK4 mRNA level (with peritumor mRNA sample as control) was significantly higher in the tumor specimens, via the two-tailed paired t test (p < 0.0001, R2 = 1802, 95 % confidence interval (0.2545 to 0.6573)). We then re-grouped those samples according to their PAK4 levels as high PAK4 group (n = 43) and low PAK4 group (n = 50) (the patient with the relative PAK4 mRNA level higher than “1” in the tumor sample than in the peritumor sample was classified into the high PAK4 group), and the unpaired t test indicated a significant difference between the two group (p < 0.0001, Fig. 1b).Fig. 1


PAK4 confers the malignance of cervical cancers and contributes to the cisplatin-resistance in cervical cancer cells via PI3K/AKT pathway.

Shu XR, Wu J, Sun H, Chi LQ, Wang JH - Diagn Pathol (2015)

PAK4 is upregulated in cervical cancer specimens and associates with poor overall survival. a Upregulated PAK4 mRNA level in the intra-tumor specimens than in the peritumor specimens of cervical cancer patients, with paired t test; b Increased PAK4 mRNA level in cervical cancer specimens, with unpaired t test; c Kaplan-Meier survival analysis for high PAK4 expression level (>1) versus low PAK4 expression level (≤1) in patients with cervical cancer. Statistical significance was considered when p < 0.05
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4584462&req=5

Fig1: PAK4 is upregulated in cervical cancer specimens and associates with poor overall survival. a Upregulated PAK4 mRNA level in the intra-tumor specimens than in the peritumor specimens of cervical cancer patients, with paired t test; b Increased PAK4 mRNA level in cervical cancer specimens, with unpaired t test; c Kaplan-Meier survival analysis for high PAK4 expression level (>1) versus low PAK4 expression level (≤1) in patients with cervical cancer. Statistical significance was considered when p < 0.05
Mentions: There were total of 93 cases of cervical cancer patients were involved in this study. As shown in table 1, these patients were aged from 30 to 75 year, with a median age of 53 years. The detailed tumor clinic-pathological characteristics of all patients, such as tumor size, HPV infection, tumor histology and histological grade, FIGO stage, distant and lymph node metastasis are summarized in table 1. And the PAK4 expression in mRNA level in the peritumor tissue (more than 2 cm from tumor tissue) and in tumor tissue in each patient was examined with RT-qPCR method. Figure 1 demonstrated that the relative PAK4 mRNA level (with peritumor mRNA sample as control) was significantly higher in the tumor specimens, via the two-tailed paired t test (p < 0.0001, R2 = 1802, 95 % confidence interval (0.2545 to 0.6573)). We then re-grouped those samples according to their PAK4 levels as high PAK4 group (n = 43) and low PAK4 group (n = 50) (the patient with the relative PAK4 mRNA level higher than “1” in the tumor sample than in the peritumor sample was classified into the high PAK4 group), and the unpaired t test indicated a significant difference between the two group (p < 0.0001, Fig. 1b).Fig. 1

Bottom Line: In addition, the PI3K/Akt pathway has been implicated in the PAK4-confered cisplatin resistance.And the PI3K/Akt inhibitor, LY294002, markedly deteriorated the cisplatin-mediated viability reduction of Hela or Caski cells, indicating the involvement of PI3K/Akt pathway in the cisplatin resistance in cervical cancer cells.This study has confirmed the significant prognostic role of PAK4 level in cervical cancer patients and has recognized the regulatory role in cervical cancer progression.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical Science and Technology, Tianjin University, No. 92, Weijin Road, Nankai District, Tianjin, 300072, China.

ABSTRACT

Background: Multiple protein or microRNA markers have been recognized to contribute to the progression and recurrence of cervical cancers. Particular those, which are associated with the chemo- or radio-resistance of cervical cancers, have been proposed to be promising and to facilitate the definition for cervical cancer treatment options.

Methods: This study was designed to explore the potential prognosis value of p21-activated kinase (PAK)-4 in cervical cancer, via the Kaplan-Meier analysis, log-rank test and Cox regression analysis, and then to investigate the regulatory role of PAK4 in the cisplatin resistance in cervical cancer cells, via the strategies of both PAK4 overexpression and PAK4 knockout.

Results: It was demonstrated that PAK4 was upregulated in cervical cancer tissues, in an association with the cancer's malignance variables such as FIGO stage, lymph node or distant metastasis and the poor histological grade. The high PAK4 expression was also independently associated with poor prognosis to cervical cancer patients. Moreover, PAK4 confers cisplatin resistance in cervical cancer Hela or Caski cells. In addition, the PI3K/Akt pathway has been implicated in the PAK4-confered cisplatin resistance. And the PI3K/Akt inhibitor, LY294002, markedly deteriorated the cisplatin-mediated viability reduction of Hela or Caski cells, indicating the involvement of PI3K/Akt pathway in the cisplatin resistance in cervical cancer cells.

Conclusion: This study has confirmed the significant prognostic role of PAK4 level in cervical cancer patients and has recognized the regulatory role in cervical cancer progression. Moreover, our study has indicated that PAK4 also confers the chemoresistance of cervical cancer cells in a PI3K/Akt-dependent way. Thus, our study indicates PAK4 as a promising marker for cervical cancer treatment.

No MeSH data available.


Related in: MedlinePlus