Actin like-6A promotes glioma progression through stabilization of transcriptional regulators YAP/TAZ

Abstract

Increased Actin-like 6A (ACTL6A) expression has been implicated in the development of diverse cancers and recently associated with the Hippo signaling pathway, which is known to regulate biological properties, including proliferation, tissue regeneration, stem cell biology, as well as tumorigenesis. Here we first show that ACTL6A is upregulated in human gliomas and its expression is associated with glioma patient survival. ACTL6A promotes malignant behaviors of glioma cells in vitro and in orthotopic xenograft model. In co-immunoprecipitation assays, we discover that ACTL6A physically associated with YAP/TAZ and furthermore disrupts the interaction between YAP and β-TrCP E3 ubiquitin ligase, which promotes YAP protein degradation. Moreover, effects of ACTL6A on glioma cells proliferation, migration, and invasion could be mediated by YAP/TAZ. These data indicate that ACTL6A may contribute to cancer progression by stabilizing YAP/TAZ and therefore provide a novel therapeutic target for the treatment of human gliomas.

MiR‐216a‐3p suppresses the proliferation and invasion of cervical cancer through downregulation of ACTL6A‐mediated YAP signaling

“…Our study confirmed ACTL6A as a critical regulator for YAP/TAZ in cervical cancer. Our findings are consistent with previous studies that revealed ACTL6A is essential for driving the activation of YAP/TAZ‐mediated transcription (Ji et al, 2018; Saladi et al, 2017). ACTL6A collaborates with p63 to decrease pYAP and enhance YAP/TAZ‐mediated transcriptional activity (Saladi et al, 2017).…”

MiR‐216a‐3p suppresses the proliferation and invasion of cervical cancer through downregulation of ACTL6A‐mediated YAP signaling

“…Our study confirmed ACTL6A as a critical regulator for YAP/TAZ in cervical cancer. Our findings are consistent with previous studies that revealed ACTL6A is essential for driving the activation of YAP/TAZ‐mediated transcription (Ji et al, 2018; Saladi et al, 2017). ACTL6A collaborates with p63 to decrease pYAP and enhance YAP/TAZ‐mediated transcriptional activity (Saladi et al, 2017).…”

A Comprehensive Analysis Revealing FBXW9 as a Potential Prognostic and Immunological Biomarker in Breast Cancer

“…According to data from breast cancer, it was found that most FBXWs were negatively correlated with stemness except FBXW5 and 9, which were positively correlated with cancer stemness. Consistent with our findings, FBXW1 was verified as an E3 ligase mediating TAZ/YAP degradation, and, thus, contributed to the initiation property and drug resistance of cancer cells [ 31 , 32 ]. Additionally, FBXW9 was positively correlated with the activity of MYC signaling according to RABIT transcription factor regulatory impact, which is a well-known contributor to cancer stemness [ 33 ].…”

Long Noncoding RNA SChLAP1 Forms a Growth-Promoting Complex with HNRNPL in Human Glioblastoma through Stabilization of ACTN4 and Activation of NF-κB Signaling

“…However, Cy3-SChLAP1 was not detected in NHA. These results were consistent with SChLAP1 localization in human prostate cancer cells (13). We further validated these results by performing qRT-PCR on nuclear and cytoplasmic fractions of RNA obtained from these cell populations.…”

MiR‐216a‐3p suppresses the proliferation and invasion of cervical cancer through downregulation of ACTL6A‐mediated YAP signaling

“…Our study confirmed ACTL6A as a critical regulator for YAP/TAZ in cervical cancer. Our findings are consistent with previous studies that revealed ACTL6A is essential for driving the activation of YAP/TAZ‐mediated transcription (Ji et al, 2018; Saladi et al, 2017). ACTL6A collaborates with p63 to decrease pYAP and enhance YAP/TAZ‐mediated transcriptional activity (Saladi et al, 2017).…”

A Comprehensive Analysis Revealing FBXW9 as a Potential Prognostic and Immunological Biomarker in Breast Cancer

“…According to data from breast cancer, it was found that most FBXWs were negatively correlated with stemness except FBXW5 and 9, which were positively correlated with cancer stemness. Consistent with our findings, FBXW1 was verified as an E3 ligase mediating TAZ/YAP degradation, and, thus, contributed to the initiation property and drug resistance of cancer cells [ 31 , 32 ]. Additionally, FBXW9 was positively correlated with the activity of MYC signaling according to RABIT transcription factor regulatory impact, which is a well-known contributor to cancer stemness [ 33 ].…”

Long Noncoding RNA SChLAP1 Forms a Growth-Promoting Complex with HNRNPL in Human Glioblastoma through Stabilization of ACTN4 and Activation of NF-κB Signaling

“…However, Cy3-SChLAP1 was not detected in NHA. These results were consistent with SChLAP1 localization in human prostate cancer cells (13). We further validated these results by performing qRT-PCR on nuclear and cytoplasmic fractions of RNA obtained from these cell populations.…”

MiR‐216a‐3p suppresses the proliferation and invasion of cervical cancer through downregulation of ACTL6A‐mediated YAP signaling

“…Our study confirmed ACTL6A as a critical regulator for YAP/TAZ in cervical cancer. Our findings are consistent with previous studies that revealed ACTL6A is essential for driving the activation of YAP/TAZ‐mediated transcription (Ji et al, 2018; Saladi et al, 2017). ACTL6A collaborates with p63 to decrease pYAP and enhance YAP/TAZ‐mediated transcriptional activity (Saladi et al, 2017).…”

A Comprehensive Analysis Revealing FBXW9 as a Potential Prognostic and Immunological Biomarker in Breast Cancer

“…According to data from breast cancer, it was found that most FBXWs were negatively correlated with stemness except FBXW5 and 9, which were positively correlated with cancer stemness. Consistent with our findings, FBXW1 was verified as an E3 ligase mediating TAZ/YAP degradation, and, thus, contributed to the initiation property and drug resistance of cancer cells [ 31 , 32 ]. Additionally, FBXW9 was positively correlated with the activity of MYC signaling according to RABIT transcription factor regulatory impact, which is a well-known contributor to cancer stemness [ 33 ].…”

Long Noncoding RNA SChLAP1 Forms a Growth-Promoting Complex with HNRNPL in Human Glioblastoma through Stabilization of ACTN4 and Activation of NF-κB Signaling

“…However, Cy3-SChLAP1 was not detected in NHA. These results were consistent with SChLAP1 localization in human prostate cancer cells (13). We further validated these results by performing qRT-PCR on nuclear and cytoplasmic fractions of RNA obtained from these cell populations.…”