IQ motif-containing GTPase-activating protein 2 inhibits breast cancer angiogenesis by suppressing VEGFR2-AKT signaling

IQ motif-containing GTPase-activating protein 3 (IQGAP3), the latest found IQGAP family protein, may act as a crucial factor in the process of cancer development and progression; however, its clinical value in breast cancer remains unestablished so far. Our team explored the correlation between the IQGAP3 expression profile and clinicopathological features in breast cancer. IQGAP3 levels in breast cancer cell lines and tumor tissues were detected through real-time PCR and western blotting. We evaluated IQGAP3 expression in archived paraffin-embedded tissue specimens of 257 breast cancer patients, and determined the relationship between IQGAP3 expression and sensitivity to radiation therapy (RT), using subgroup analysis. We also analyzed the association between IQGAP3 expression and the clinical characters and prognosis of breast cancer. There was a significant upregulation of IQGAP3 in breast cancer cell lines and human tumor tissues at both mRNA and protein levels. In addition, 42.8% of the breast cancer specimens had high expression of IQGAP3, which was significantly related to clinical stage (P = 0.001), T category (P = 0.002), N category (P = 0.001), locoregional recurrence (P = 0.002), distant metastasis (P = 0.001), and vital status (P = 0.001). Univariate and multivariate statistical analyses showed that IQGAP3 is an independent prognostic factor for all the breast cancer patients (P = 0.003, P = 0.001). Subgroup analysis revealed that IQGAP3 expression is correlated with radiation therapy resistance and is an independent predictor for radiation therapy outcome. Our findings suggest that IQGAP3 may be a reliable novel biomarker to provide personalized prognosis and identify patients who can profit from a more aggressive RT regimen for improving breast cancer patient survival.

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RNA Interference of IQ Motif Containing GTPase-Activating Protein 3 (IQGAP3) Inhibits Cell Proliferation and Invasion in Breast Carcinoma Cells

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504016x14685034103635 ◽

2016 ◽

Vol 24 (6) ◽

pp. 455-461 ◽

Cited By ~ 11

Author(s):

Gaowu Hu ◽

Ye Xu ◽

Wenquan Chen ◽

Jiandong Wang ◽

Chunying Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Rna Interference ◽

Cancer Cell ◽

Migration And Invasion ◽

Mrna Levels ◽

Gtpase Activating Protein ◽

Iq Motif ◽

Proliferation And Metastasis ◽

Cell Proliferation And Metastasis

Breast cancer is a highly prevalent disease affecting women. The association of IQ motif containing GTPase-activating protein 3 (IQGAP3) and breast cancer is poorly defined. Here we reported that IQGAP3 is a key regulator of cell proliferation and metastasis during breast cancer progression. The expression of IQGAP3 was significantly increased in breast tissues compared to nontumor tissues at both protein and mRNA levels. Furthermore, IQGAP3 had a high expression level in ZR-75-30 and BT474 compared to other breast cancer cell lines. Depletion of IQGAP3 through RNA interference in ZR-75-30 and BT474 significantly inhibited cell proliferation. More importantly, IQGAP3 silencing in breast cancer cells notably repressed cell migration and invasion. Further analysis suggested that inhibition of cell proliferation and metastasis was associated with some proteins, including p53, MMP9, Snail, CDC42, p-ERK1/2, KIF2C, KIF4A, PCNA, and Twist. Since expression of IQGAP3 seems to be associated with the pathogenesis of breast cancer and suppression of it can inhibit cancer cell growth and metastasis, IQGAP3 may be a potential therapeutic target in human breast cancer.

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Effects of deguelin on proliferation and apoptosis of MCF-7 breast cancer cells by phosphatidylinositol 3-kinase/Akt signaling pathway

Journal of Chinese Integrative Medicine ◽

10.3736/jcim20110511 ◽

2011 ◽

Vol 9 (5) ◽

pp. 533-538 ◽

Cited By ~ 9

Author(s):

ZH Chu

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Breast Cancer Cells ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Phosphatidylinositol 3 Kinase ◽

Proliferation And Apoptosis ◽

Mcf 7 ◽

Phosphatidylinositol 3

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Breast Cancer Chemoresistance Mechanisms Through PI 3-Kinase and Akt Signaling

10.21236/ada608893 ◽

2014 ◽

Author(s):

Alex Toker ◽

Kristin Brown

Keyword(s):

Breast Cancer ◽

Akt Signaling ◽

Cancer Chemoresistance

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INPP4B promotes PI3Kα-dependent late endosome formation and Wnt/β-catenin signaling in breast cancer

Nature Communications ◽

10.1038/s41467-021-23241-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Samuel J. Rodgers ◽

Lisa M. Ooms ◽

Viola M. J. Oorschot ◽

Ralf B. Schittenhelm ◽

Elizabeth V. Nguyen ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

Breast Cancer Cells ◽

Triple Negative ◽

Akt Signaling ◽

Late Endosome ◽

Breast Cancers ◽

Lysosomal Degradation ◽

Late Endosomes ◽

Mrna And Protein Expression

AbstractINPP4B suppresses PI3K/AKT signaling by converting PI(3,4)P2 to PI(3)P and INPP4B inactivation is common in triple-negative breast cancer. Paradoxically, INPP4B is also a reported oncogene in other cancers. How these opposing INPP4B roles relate to PI3K regulation is unclear. We report PIK3CA-mutant ER+ breast cancers exhibit increased INPP4B mRNA and protein expression and INPP4B increased the proliferation and tumor growth of PIK3CA-mutant ER+ breast cancer cells, despite suppression of AKT signaling. We used integrated proteomics, transcriptomics and imaging to demonstrate INPP4B localized to late endosomes via interaction with Rab7, which increased endosomal PI3Kα-dependent PI(3,4)P2 to PI(3)P conversion, late endosome/lysosome number and cargo trafficking, resulting in enhanced GSK3β lysosomal degradation and activation of Wnt/β-catenin signaling. Mechanistically, Wnt inhibition or depletion of the PI(3)P-effector, Hrs, reduced INPP4B-mediated cell proliferation and tumor growth. Therefore, INPP4B facilitates PI3Kα crosstalk with Wnt signaling in ER+ breast cancer via PI(3,4)P2 to PI(3)P conversion on late endosomes, suggesting these tumors may be targeted with combined PI3K and Wnt/β-catenin therapies.

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