PAK5 facilitates the proliferation, invasion and migration in colorectal cancer cells

被引:16
作者
Huang, Silin [1 ]
Zhu, Ying [1 ]
Wang, Chunfei [2 ]
Li, Xiaxi [1 ]
Cui, Xiaobing [1 ]
Tu, Sufang [1 ]
You, Lijuan [1 ]
Fu, JingWen [1 ]
Chen, Zemin [1 ]
Hu, Wei [1 ,3 ]
Gong, Wei [1 ]
机构
[1] Southern Med Univ, Dept Gastroenterol, Shenzhen Hosp, Shenzhen, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Endoscopy Ctr, Affiliated Hosp 7, Shenzhen, Guangdong, Peoples R China
[3] Chinese Univ Hong Kong, Dept Anaesthesia & Intens Care, Hong Kong, Peoples R China
来源
CANCER MEDICINE | 2020年 / 9卷 / 13期
基金
中国国家自然科学基金;
关键词
colorectal cancer; invasion; migration; PAK5; proliferation; P21-ACTIVATED KINASE-5; FOCAL ADHESIONS; PROTECTS CELLS; ACTIN; PROGRESSION; ACTIVATION; APOPTOSIS; MOTILITY; GROWTH; RAF-1;
D O I
10.1002/cam4.3084
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Colorectal cancer (CRC) is the third-most common cancer around the world, accounting for approximately 10% of cancer-related mortality. Deeper molecular understanding of colorectal carcinogenesis will provide evidences for identification of early diagnostic indicators and novel therapeutic strategies for CRC treatment. The p21(cdc42/rac1)-activated kinase 5 (PAK5) has been reported to be involved in a variety of tumor-promoting behaviors, whereas the underlying mechanisms of PAK5 in CRC progression are still obscure. Our current study revealed an upregulated expression of PAK5 in human CRC tissues as compared with normal adjacent biopsies, which was associated with tumor progression and metastasis. We further unraveled that inhibition of PAK5 was correlated with restrained proliferation, migration, and invasion of CRC cells in vitro and in vivo. Moreover, we showed an indispensable role of PAK5 in interacting with Cdc42 and Integrin beta 1, beta 3, thus, to facilitate the migration and invasion of CRC cells. Collectively, we pointed out a potential of PAK5 to serve as a novel therapeutic target in restricting CRC proliferation and metastasis. The uncovered mechanisms will deepen the comprehension with regard to the mechanisms of CRC progression, as well as providing new insights for therapeutic intervention in colorectal cancer.
引用
收藏
页码:4777 / 4790
页数:14
相关论文
共 55 条
[1]   Role of surgery in colorectal cancer liver metastases [J].
Akgul, Ozgur ;
Cetinkaya, Erdinc ;
Ersoz, Siyar ;
Tez, Mesut .
WORLD JOURNAL OF GASTROENTEROLOGY, 2014, 20 (20) :6113-6122
[2]   The integrin-binding protein Nischarin regulates cell migration by inhibiting PAK [J].
Alahari, SK ;
Reddig, PJ ;
Juliano, RL .
EMBO JOURNAL, 2004, 23 (14) :2777-2788
[3]   Colorectal Cancer: Epidemiology, Disease Mechanisms and Interventions to Reduce Onset and Mortality [J].
Aran, Veronica ;
Victorino, Ana Paula ;
Thuler, Luiz Claudio ;
Ferreira, Carlos Gil .
CLINICAL COLORECTAL CANCER, 2016, 15 (03) :195-203
[4]   PAK to the future [J].
Bagrodia, S ;
Cerione, RA .
TRENDS IN CELL BIOLOGY, 1999, 9 (09) :350-355
[5]   Rho GTPases and their effector proteins [J].
Bishop, AL ;
Hall, A .
BIOCHEMICAL JOURNAL, 2000, 348 (02) :241-255
[6]   Biology of the p21-activated kinases [J].
Bokoch, GM .
ANNUAL REVIEW OF BIOCHEMISTRY, 2003, 72 :743-781
[7]   BEAUTY [J].
Brody, Herb .
NATURE, 2015, 526 (7572) :S1-S1
[8]   Requirement for PAK4 in the anchorage-independent growth of human cancer cell lines [J].
Callow, MG ;
Clairvoyant, F ;
Zhu, S ;
Schryver, B ;
Whyte, DB ;
Bischoff, JR ;
Jallal, B ;
Smeal, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (01) :550-558
[9]   Control of actin dynamics in cell motility - Role of ADF/cofilin [J].
Carlier, MF ;
Ressad, F ;
Pantaloni, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (48) :33827-33830
[10]   Pak-1 expression increases with progression of colorectal carcinomas to metastasis [J].
Carter, JH ;
Douglass, LE ;
Deddens, JA ;
Colligan, BM ;
Bhatt, TR ;
Pemberton, JO ;
Konicek, S ;
Hom, J ;
Marshall, M ;
Graff, JR .
CLINICAL CANCER RESEARCH, 2004, 10 (10) :3448-3456