Patient derived mutation W257G of PPP2R1A enhances cancer cell migration through SRC-JNK-c-Jun pathway

Ae Lee Jeong, Sora Han, Sunyi Lee, Jeong Su Park, Yiling Lu, Shuangxing Yu, Jane Li, Kyung Hee Chun, Gordon Mills, Young Yang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Mutation of PPP2R1A has been observed at high frequency in endometrial serous carcinomas but at low frequency in ovarian clear cell carcinoma. However, the biological role of mutation of PPP2R1A in ovarian and endometrial cancer progression remains unclear. In this study, we found that PPP2R1A expression is elevated in high-grade primary tumor patients with papillary serous tumors of the ovary. To determine whether increased levels or mutation of PPP2R1A might contribute to cancer progression, the effects of overexpression or mutation of PPP2R1A on cell proliferation, migration, and PP2A phosphatase activity were investigated using ovarian and endometrial cancer cell lines. Among the mutations, PPP2R1A-W257G enhanced cell migration in vitro through activating SRC-JNK-c-Jun pathway. Overexpression of wild type (WT) PPP2R1A increased its binding ability with B56 regulatory subunits, whereas PPP2R1A-mutations lost the ability to bind to most B56 subunits except B56δ. Total PP2A activity and PPP2R1A-Associated PP2Ac activity were significantly increased in cells overexpressing PPP2R1A-WT. In addition, overexpression of PPP2R1A-WT increased cell proliferation in vitro and tumor growth in vivo.

Original languageEnglish (US)
Article number27391
JournalScientific Reports
Volume6
DOIs
StatePublished - Jun 7 2016
Externally publishedYes

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Cell Movement
Mutation
Endometrial Neoplasms
Neoplasms
Ovarian Neoplasms
Cell Proliferation
Phosphoric Monoester Hydrolases
Ovary
Carcinoma
Cell Line
Growth
In Vitro Techniques

ASJC Scopus subject areas

  • General

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Patient derived mutation W257G of PPP2R1A enhances cancer cell migration through SRC-JNK-c-Jun pathway. / Jeong, Ae Lee; Han, Sora; Lee, Sunyi; Su Park, Jeong; Lu, Yiling; Yu, Shuangxing; Li, Jane; Chun, Kyung Hee; Mills, Gordon; Yang, Young.

In: Scientific Reports, Vol. 6, 27391, 07.06.2016.

Research output: Contribution to journalArticle

Jeong, Ae Lee ; Han, Sora ; Lee, Sunyi ; Su Park, Jeong ; Lu, Yiling ; Yu, Shuangxing ; Li, Jane ; Chun, Kyung Hee ; Mills, Gordon ; Yang, Young. / Patient derived mutation W257G of PPP2R1A enhances cancer cell migration through SRC-JNK-c-Jun pathway. In: Scientific Reports. 2016 ; Vol. 6.
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abstract = "Mutation of PPP2R1A has been observed at high frequency in endometrial serous carcinomas but at low frequency in ovarian clear cell carcinoma. However, the biological role of mutation of PPP2R1A in ovarian and endometrial cancer progression remains unclear. In this study, we found that PPP2R1A expression is elevated in high-grade primary tumor patients with papillary serous tumors of the ovary. To determine whether increased levels or mutation of PPP2R1A might contribute to cancer progression, the effects of overexpression or mutation of PPP2R1A on cell proliferation, migration, and PP2A phosphatase activity were investigated using ovarian and endometrial cancer cell lines. Among the mutations, PPP2R1A-W257G enhanced cell migration in vitro through activating SRC-JNK-c-Jun pathway. Overexpression of wild type (WT) PPP2R1A increased its binding ability with B56 regulatory subunits, whereas PPP2R1A-mutations lost the ability to bind to most B56 subunits except B56δ. Total PP2A activity and PPP2R1A-Associated PP2Ac activity were significantly increased in cells overexpressing PPP2R1A-WT. In addition, overexpression of PPP2R1A-WT increased cell proliferation in vitro and tumor growth in vivo.",
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AU - Lu, Yiling

AU - Yu, Shuangxing

AU - Li, Jane

AU - Chun, Kyung Hee

AU - Mills, Gordon

AU - Yang, Young

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