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Reduced IQGAP2 expression promotes EMT and inhibits apoptosis by modulating the MEK-ERK and p38 signaling in breast cancer irrespective of ER status.
Kumar, Dinesh; Patel, Saket Awadesbhai; Hassan, Md Khurshidul; Mohapatra, Nachiketa; Pattanaik, Niharika; Dixit, Manjusha.
Afiliación
  • Kumar D; School of Biological Sciences, National Institute of Science Education and Research Bhubaneswar, HBNI, P.O. Jatni, Khurda, Odisha, 752050, India.
  • Patel SA; School of Biological Sciences, National Institute of Science Education and Research Bhubaneswar, HBNI, P.O. Jatni, Khurda, Odisha, 752050, India.
  • Hassan MK; School of Biological Sciences, National Institute of Science Education and Research Bhubaneswar, HBNI, P.O. Jatni, Khurda, Odisha, 752050, India.
  • Mohapatra N; Apollo Hospitals, Plot No. 251, Old Sainik School Road, Bhubaneswar, Odisha, 750015, India.
  • Pattanaik N; AMRI Hospital, Plot No. 1, Near Jayadev Vatika Park, Khandagiri, Bhubaneswar, Odisha, 751019, India.
  • Dixit M; School of Biological Sciences, National Institute of Science Education and Research Bhubaneswar, HBNI, P.O. Jatni, Khurda, Odisha, 752050, India. manjusha@niser.ac.in.
Cell Death Dis ; 12(4): 389, 2021 04 12.
Article en En | MEDLINE | ID: mdl-33846302
IQGAP2, a member of the IQGAP family, functions as a tumor suppressor in most of the cancers. Unlike IQGAP1 and IQGAP3, which function as oncogenes in breast cancer, the role of IQGAP2 is still unexplored. Here we report a reduced expression of IQGAP2, which was associated with lymph node positivity, lymphovascular invasion, and higher age in breast cancer patients. We found an inverse correlation of IQGAP2 expression levels with oncogenic properties of breast cancer cell lines in estrogen receptor (ER) independent manner. IQGAP2 expression enhanced apoptosis via reactive oxygen species (ROS)-P38-p53 pathway and reduced epithelial-mesenchymal transition (EMT) in a MEK-ERK-dependent manner. IQGAP2-IQGAP1 ratio correlated negatively with phospho-ERK levels in breast cancer patients. Pull-down assay showed interaction of IQGAP1 and IQGAP2. IQGAP2 overexpression rescued, IQGAP1-mediated ERK activation, suggesting the possibility of IQGAP1 sequestration by IQGAP2. IQGAP2 depletion, in a tumor xenograft model, increased tumor volume, tumor weight, and phospho-ERK expression. Overall, our findings suggest that IQGAP2 is negatively associated with proliferative and metastatic abilities of breast cancer cells. Suppression of IQGAP1-mediated ERK activation is a possible route via which IQGAP2 restricts oncogenic properties of breast cancer cells. Our study highlights the candidature of IQGAP2 as a potent target for therapeutic intervention.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Receptores de Estrógenos / Sistema de Señalización de MAP Quinasas / Proteínas Activadoras de ras GTPasa Tipo de estudio: Prognostic_studies Límite: Adult / Animals / Female / Humans Idioma: En Revista: Cell Death Dis Año: 2021 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Receptores de Estrógenos / Sistema de Señalización de MAP Quinasas / Proteínas Activadoras de ras GTPasa Tipo de estudio: Prognostic_studies Límite: Adult / Animals / Female / Humans Idioma: En Revista: Cell Death Dis Año: 2021 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido