PRICKLE1 Contributes to Cancer Cell Dissemination through Its Interaction with mTORC2

被引：66

作者：

Daulat, Avais M. ^{[1
,2
,3
,4
]}

Bertucci, Francois ^{[2
,3
,4
,5
]}

Audebert, Stephane ^{[1
,2
,3
,4
]}

Serge, Arnauld ^{[2
,3
,4
,6
]}

Finetti, Pascal ^{[2
,3
,4
,5
]}

Josselin, Emmanuelle ^{[2
,3
,4
,7
]}

Castellano, Remy ^{[2
,3
,4
,7
]}

Birnbaum, Daniel ^{[2
,3
,4
,5
]}

Angers, Stephane ^{[8
,9
]}

Borg, Jean-Paul ^{[1
,2
,3
,4
]}

机构：

[1] Cell Polar Cell Signalling & Canc Equipe Labellis, CRCM, INSERM, U1068, F-13009 Marseille, France

[2] Inst J Paoli I Calmettes, F-13009 Marseille, France

[3] Aix Marseille Univ, UM 105, F-13284 Marseille, France

[4] CRCM, CNRS, UMR7258, F-13009 Marseille, France

[5] Mol Oncol Equipe Labellise Ligue Canc, INSERM, U1068, F-13009 Marseille, France

[6] CRCM, Leuko Stromal Interact, INSERM, U1068, F-13009 Marseille, France

[7] CRCM, TrGET Platform, INSERM, U1068, F-13009 Marseille, France

[8] Univ Toronto, Dept Pharmaceut Sci, Leslie Dan Fac Pharm, Toronto, ON M5S3M2, Canada

[9] Univ Toronto, Fac Med, Dept Biochem, 100 Coll St, Toronto, ON M5S 1A8, Canada

来源：

DEVELOPMENTAL CELL | 2016年 / 37卷 / 04期

关键词：

DEPENDENT MANNER; PLANAR POLARITY; FOCAL ADHESIONS; MELANOMA-CELLS; MIGRATION; PATHWAY; COMPLEX; KINASE; ACTIVATION; MOTILITY;

D O I：

10.1016/j.devcel.2016.04.011

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Components of the evolutionarily conserved developmental planar cell polarity (PCP) pathway were recently described to play a prominent role in cancer cell dissemination. However, the molecular mechanisms by which PCP molecules drive the spread of cancer cells remain largely unknown. PRICKLE1 encodes a PCP protein bound to the promigratory serine/threonine kinase MINK1. We identify RICTOR, a member of the mTORC2 complex, as a PRICKLE1-binding partner and show that the integrity of the PRICKLE1-MINK1-RICTOR complex is required for activation of AKT, regulation of focal adhesions, and cancer cell migration. Disruption of the PRICKLE1-RICTOR interaction results in a strong impairment of breast cancer cell dissemination in xenograft assays. Finally, we show that upregulation of PRICKLE1 in basal breast cancers, a subtype characterized by high metastatic potential, is associated with poor metastasis-free survival.

引用

页码：311 / 325

页数：15

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