Integrity of SOS1/EPS8/ABI1 tri-complex determines ovarian cancer metastasis

Huijun Chen, Xufeng Wu, Zhixing K. Pan, Shuang Huang

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Ovarian cancer is mainly confined in peritoneal cavity and its metastasis is often associated with the formation of malignant ascites. As lysophosphatidic acid (LPA) is present at high levels in ascites of ovarian cancer patients and potently stimulates cell migration, we reason that LPA-stimulated cell migration may play an important role in ovarian cancer metastasis. Here, we show that only ovarian cancer cell lines with LPA migratory response undergo peritoneal metastatic colonization. LPA-stimulated cell migration is required for metastatic colonization because knockdown of LPA receptor subtype 1 (LPAR1) abolishes this event. However, the difference in metastatic potentials is not caused by the absence of LPAR1 because both metastatic and nonmetastatic lines express similar levels of LPAR1. Instead, we find that LPA can activate Rac only in metastatic cells and that metastatic colonization of ovarian cancer cells necessitates Rac activity. These results thus suggest that LPA-induced Rac activation is a prerequisite for ovarian cancer metastasis. In metastatic cells, Rac activation is facilitated by SOS1/EPS8/ABI1 tri-complex and the integrity of this tri-complex is essential for LPAstimulated cell migration and metastatic colonization. We show that at least 1 member of SOS1/EPS8/ABI1 tricomplex is absent in nonmetastatic ovarian cancer cells and reexpressing the missing one conferred them with metastatic capability. Importantly, coexpression of SOS1, EPS8, and ABI1, but not of any individual member of SOS1/EPS8/ABI1 tri-complex, correlates with advanced stages and shorter survival of ovarian cancer patients. Our study implicates that the integrity of SOS1/EPS8/ABI1 tri-complex is a determinant of ovarian cancer metastasis.

Original languageEnglish (US)
Pages (from-to)9979-9990
Number of pages12
JournalCancer Research
Volume70
Issue number23
DOIs
StatePublished - Dec 1 2010

Fingerprint

Ovarian Neoplasms
Neoplasm Metastasis
Lysophosphatidic Acid Receptors
Cell Movement
Ascites
Peritoneal Cavity
lysophosphatidic acid
Cell Line
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Integrity of SOS1/EPS8/ABI1 tri-complex determines ovarian cancer metastasis. / Chen, Huijun; Wu, Xufeng; Pan, Zhixing K.; Huang, Shuang.

In: Cancer Research, Vol. 70, No. 23, 01.12.2010, p. 9979-9990.

Research output: Contribution to journalArticle

Chen, Huijun ; Wu, Xufeng ; Pan, Zhixing K. ; Huang, Shuang. / Integrity of SOS1/EPS8/ABI1 tri-complex determines ovarian cancer metastasis. In: Cancer Research. 2010 ; Vol. 70, No. 23. pp. 9979-9990.
@article{211ef8b046a24b3da55df19bb0d105ca,
title = "Integrity of SOS1/EPS8/ABI1 tri-complex determines ovarian cancer metastasis",
abstract = "Ovarian cancer is mainly confined in peritoneal cavity and its metastasis is often associated with the formation of malignant ascites. As lysophosphatidic acid (LPA) is present at high levels in ascites of ovarian cancer patients and potently stimulates cell migration, we reason that LPA-stimulated cell migration may play an important role in ovarian cancer metastasis. Here, we show that only ovarian cancer cell lines with LPA migratory response undergo peritoneal metastatic colonization. LPA-stimulated cell migration is required for metastatic colonization because knockdown of LPA receptor subtype 1 (LPAR1) abolishes this event. However, the difference in metastatic potentials is not caused by the absence of LPAR1 because both metastatic and nonmetastatic lines express similar levels of LPAR1. Instead, we find that LPA can activate Rac only in metastatic cells and that metastatic colonization of ovarian cancer cells necessitates Rac activity. These results thus suggest that LPA-induced Rac activation is a prerequisite for ovarian cancer metastasis. In metastatic cells, Rac activation is facilitated by SOS1/EPS8/ABI1 tri-complex and the integrity of this tri-complex is essential for LPAstimulated cell migration and metastatic colonization. We show that at least 1 member of SOS1/EPS8/ABI1 tricomplex is absent in nonmetastatic ovarian cancer cells and reexpressing the missing one conferred them with metastatic capability. Importantly, coexpression of SOS1, EPS8, and ABI1, but not of any individual member of SOS1/EPS8/ABI1 tri-complex, correlates with advanced stages and shorter survival of ovarian cancer patients. Our study implicates that the integrity of SOS1/EPS8/ABI1 tri-complex is a determinant of ovarian cancer metastasis.",
author = "Huijun Chen and Xufeng Wu and Pan, {Zhixing K.} and Shuang Huang",
year = "2010",
month = "12",
day = "1",
doi = "10.1158/0008-5472.CAN-10-2394",
language = "English (US)",
volume = "70",
pages = "9979--9990",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "23",

}

TY - JOUR

T1 - Integrity of SOS1/EPS8/ABI1 tri-complex determines ovarian cancer metastasis

AU - Chen, Huijun

AU - Wu, Xufeng

AU - Pan, Zhixing K.

AU - Huang, Shuang

PY - 2010/12/1

Y1 - 2010/12/1

N2 - Ovarian cancer is mainly confined in peritoneal cavity and its metastasis is often associated with the formation of malignant ascites. As lysophosphatidic acid (LPA) is present at high levels in ascites of ovarian cancer patients and potently stimulates cell migration, we reason that LPA-stimulated cell migration may play an important role in ovarian cancer metastasis. Here, we show that only ovarian cancer cell lines with LPA migratory response undergo peritoneal metastatic colonization. LPA-stimulated cell migration is required for metastatic colonization because knockdown of LPA receptor subtype 1 (LPAR1) abolishes this event. However, the difference in metastatic potentials is not caused by the absence of LPAR1 because both metastatic and nonmetastatic lines express similar levels of LPAR1. Instead, we find that LPA can activate Rac only in metastatic cells and that metastatic colonization of ovarian cancer cells necessitates Rac activity. These results thus suggest that LPA-induced Rac activation is a prerequisite for ovarian cancer metastasis. In metastatic cells, Rac activation is facilitated by SOS1/EPS8/ABI1 tri-complex and the integrity of this tri-complex is essential for LPAstimulated cell migration and metastatic colonization. We show that at least 1 member of SOS1/EPS8/ABI1 tricomplex is absent in nonmetastatic ovarian cancer cells and reexpressing the missing one conferred them with metastatic capability. Importantly, coexpression of SOS1, EPS8, and ABI1, but not of any individual member of SOS1/EPS8/ABI1 tri-complex, correlates with advanced stages and shorter survival of ovarian cancer patients. Our study implicates that the integrity of SOS1/EPS8/ABI1 tri-complex is a determinant of ovarian cancer metastasis.

AB - Ovarian cancer is mainly confined in peritoneal cavity and its metastasis is often associated with the formation of malignant ascites. As lysophosphatidic acid (LPA) is present at high levels in ascites of ovarian cancer patients and potently stimulates cell migration, we reason that LPA-stimulated cell migration may play an important role in ovarian cancer metastasis. Here, we show that only ovarian cancer cell lines with LPA migratory response undergo peritoneal metastatic colonization. LPA-stimulated cell migration is required for metastatic colonization because knockdown of LPA receptor subtype 1 (LPAR1) abolishes this event. However, the difference in metastatic potentials is not caused by the absence of LPAR1 because both metastatic and nonmetastatic lines express similar levels of LPAR1. Instead, we find that LPA can activate Rac only in metastatic cells and that metastatic colonization of ovarian cancer cells necessitates Rac activity. These results thus suggest that LPA-induced Rac activation is a prerequisite for ovarian cancer metastasis. In metastatic cells, Rac activation is facilitated by SOS1/EPS8/ABI1 tri-complex and the integrity of this tri-complex is essential for LPAstimulated cell migration and metastatic colonization. We show that at least 1 member of SOS1/EPS8/ABI1 tricomplex is absent in nonmetastatic ovarian cancer cells and reexpressing the missing one conferred them with metastatic capability. Importantly, coexpression of SOS1, EPS8, and ABI1, but not of any individual member of SOS1/EPS8/ABI1 tri-complex, correlates with advanced stages and shorter survival of ovarian cancer patients. Our study implicates that the integrity of SOS1/EPS8/ABI1 tri-complex is a determinant of ovarian cancer metastasis.

UR - http://www.scopus.com/inward/record.url?scp=78649952069&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649952069&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-10-2394

DO - 10.1158/0008-5472.CAN-10-2394

M3 - Article

C2 - 21118970

AN - SCOPUS:78649952069

VL - 70

SP - 9979

EP - 9990

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 23

ER -