The RhoA dependent anti-metastatic function of RKIP in breast cancer

被引：11

作者：

Kalpana, Gardiyawasam ^{[1
]}

Figy, Christopher ^{[1
]}

Feng, Jingwei ^{[1
,3
]}

Tipton, Claire ^{[1
]}

De Castro, Julius N. ^{[1
]}

Bach, Vu N. ^{[1
]}

Borile, Clariza ^{[1
]}

LaSalla, Alexandria ^{[1
]}

Odeh, Hussain N. ^{[1
]}

Yeung, Miranda ^{[1
]}

Garcia-Mata, Rafael ^{[2
]}

Yeung, Kam C. ^{[1
]}

机构：

[1] Univ Toledo, Coll Med & Life Sci, Dept Canc Biol, Hlth Sci Campus, Toledo, OH 43614 USA

[2] Univ Toledo, Coll Nat Sci, Dept Biol Sci, Toledo, OH 43614 USA

[3] Southern Med Univ, Nanfang Hosp, Dept Plast & Cosmet Surg, 1838 Guangzhou North Rd, Guangzhou 510515, Guangdong, Peoples R China

来源：

SCIENTIFIC REPORTS | 2021年 / 11卷 / 01期

关键词：

E-CADHERIN EXPRESSION; ADHERENS JUNCTIONS; PROTEIN SUPPRESSES; KINASE-ACTIVITY; CELL-ADHESION; METASTASIS; INVASION; PATHWAY; PROGRESSION; DOWNSTREAM;

D O I：

10.1038/s41598-021-96709-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Raf-1 kinase inhibitor protein was initially discovered as a physiological kinase inhibitor of the MAPK signaling pathway and was later shown to suppress cancer cell invasion and metastasis. Yet, the molecular mechanism through which RKIP executes its effects is not completely defined. RhoA has both a pro- and anti-metastatic cell-context dependent functions. Given that Rho GTPases primarily function on actin cytoskeleton dynamics and cell movement regulation, it is possible that one way RKIP hinders cancer cell invasion/metastasis is by targeting these proteins. Here we show that RKIP inhibits cancer cell invasion and metastasis by stimulating RhoA anti-tumorigenic functions. Mechanistically, RKIP activates RhoA in an Erk2 and GEF-H1 dependent manner to enhance E-cadherin membrane localization and inhibit CCL5 expression.

引用

页数：14

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