YAP1 and PRDM14 converge to promote cell survival and tumorigenesis

Kim, Miju; Ly, Seav Huong; Xie, Yingtian; Duronio, Gina N.; Ford-Roshon, Dane; Hwang, Justin; Sulahian, Rita; Rennhack, Jonathan; So, Jonathan; Gjoerup, Ole; Talamas, Jessica A.; Grandclaudon, Maximilien; Long, Henry W.; Doench, John G.; Sethi, Nilay; Giannakis, Marios; Hahn, William C.

doi:10.1016/j.devcel.2021.12.006

Cited by 12 publications

(6 citation statements)

References 79 publications

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“…Specifically, AMOTL1 promotes the tumorigenesis via interacting with YAP1, a key factor of Hippo pathway, to induce its nuclear accumulation in gastric cancer and glioma 27,32 . As a classical transcription activator, YAP1 has been reported to act as an oncogene with tumorigenic role in the development of multiple cancers 41,42 . Generally, YAP1 translocates into nuclear to regulate downstream gene expression and its accumulation in cytoplasm leads to degradation via ubiquitin-mediated proteolysis 43 .…”

Section: Discussionmentioning

confidence: 99%

SRSF3/AMOTL1 Splicing Axis Promotes the Tumorigenesis of Nasopharyngeal Carcinoma through Regulating the Nucleus Translocation of YAP1

Jiang

Zhou

et al. 2023

Preprint

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Dysregulation of serine/arginine splicing factors (SRSFs) and thereby the abnormal alternative splicing (AS) has been widely implicated in the development of multiple cancers, but scarcely investigated in nasopharyngeal carcinoma (NPC). Here we examine the expression of 12 classical SRSFs between 87 NPC and 10 control samples, revealing a significant upregulation of SRSF3 and its association with worse prognosis in NPC. Functional assays demonstrate that SRSF3 exerts oncogenic function in NPC progression. Transcriptome analysis reveals 1 934 SRSF3-regulated AS events in genes involved in cell cycle and mRNA metabolism, among which generation of a long isoform of AMOTL1 (AMOTL1-L) is further verified through a direct bond of SRSF3 RRM domain with exon 12 of AMOTL1 to promote exon inclusion. Functional studies reveal that AMOTL1-L promotes proliferation and migration of NPC cells, while AMOTL1-S does not. Moreover, overexpression of AMOTL1-L significantly rescues the abovementioned inhibitory effects of SRSF3 knockdown, but not AMOTL1-S. Furthermore, compared with AMOTL1-S, AMOTL1-L has a localization preference in the intracellular than cell membrane, leading to a stronger interaction with YAP1 to promote its translocation to nucleus. Taken together, our findings identify SRSF3/AMOTL1 as a novel alternative splicing axis with pivotal roles in NPC development, which could be served as promising prognostic biomarkers and therapeutic targets of NPC.

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Section: Discussionmentioning

confidence: 99%

SRSF3/AMOTL1 Splicing Axis Promotes the Tumorigenesis of Nasopharyngeal Carcinoma through Regulating the Nucleus Translocation of YAP1

Jiang

Zhou

et al. 2023

Preprint

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“…Specifically, AMOTL1 promotes tumorigenesis via interacting with YAP1, a vital factor of the Hippo pathway, to induce its nuclear accumulation in gastric cancer and glioma [ 27 , 32 ]. As a classical transcription activator, YAP1 has been reported to act as an oncogene with a tumorigenic role in developing various cancers [ 42 , 43 ]. Generally, YAP1 translocates into the nucleus to regulate downstream gene expression, and its accumulation in cytoplasm leads to degradation via ubiquitin-mediated proteolysis [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

SRSF3/AMOTL1 splicing axis promotes the tumorigenesis of nasopharyngeal carcinoma through regulating the nucleus translocation of YAP1

Xu,

Jiang,

Zhou

et al. 2023

Cell Death Dis

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Dysregulation of serine/arginine splicing factors (SRSFs) and abnormal alternative splicing (AS) have been widely implicated in various cancers but scarcely investigated in nasopharyngeal carcinoma (NPC). Here we examine the expression of 12 classical SRSFs between 87 NPC and 10 control samples, revealing a significant upregulation of SRSF3 and its association with worse prognosis in NPC. Functional assays demonstrate that SRSF3 exerts an oncogenic function in NPC progression. Transcriptome analysis reveals 1,934 SRSF3-regulated AS events in genes related to cell cycle and mRNA metabolism. Among these events, we verify the generation of a long isoform of AMOTL1 (AMOTL1-L) through a direct bond of the SRSF3 RRM domain with the exon 12 of AMOTL1 to promote exon inclusion. Functional studies also reveal that AMOTL1-L promotes the proliferation and migration of NPC cells, while AMOTL1-S does not. Furthermore, overexpression of AMOTL1-L, but not -S, significantly rescues the inhibitory effects of SRSF3 knockdown. Additionally, compared with AMOTL1-S, AMOTL1-L has a localization preference in the intracellular than the cell membrane, leading to a more robust interaction with YAP1 to promote nucleus translocation. Our findings identify SRSF3/AMOTL1 as a novel alternative splicing axis with pivotal roles in NPC development, which could serve as promising prognostic biomarkers and therapeutic targets for NPC.

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“…Furthermore, CTGF and BIRC5 are identified as the direct target genes of YAP-TEAD that regulate cell growth and anti-apoptosis, respectively [ 36 ]. More interestingly, Kim et al recently showed that PRDM14-mediated transcriptional upregulation of CALM2 and SLC2A1 in colon cancers can rescue YAP suppression to sustain cell proliferation and survival [ 37 ], indicating the dominant roles of CALM2 and SLC2A1 in mediating YAP-associated cell proliferation and tumorigenesis.…”

Section: The Tumor-promoting Roles Of Yap/taz In Human Cancersmentioning

confidence: 99%

New insights into the ambivalent role of YAP/TAZ in human cancers

Luo

Deng

Zou

et al. 2023

J Exp Clin Cancer Res

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Hippo signaling was first identified in Drosophila as a key controller of organ size by regulating cell proliferation and anti-apoptosis. Subsequent studies have shown that this pathway is highly conserved in mammals, and its dysregulation is implicated in multiple events of cancer development and progression. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) (hereafter YAP/TAZ) are the downstream effectors of the Hippo pathway. YAP/TAZ overexpression or activation is sufficient to induce tumor initiation and progression, as well as recurrence and therapeutic resistance. However, there is growing evidence that YAP/TAZ also exert a tumor-suppressive function in a context-dependent manner. Therefore, caution should be taken when targeting Hippo signaling in clinical trials in the future. In this review article, we will first give an overview of YAP/TAZ and their oncogenic roles in various cancers and then systematically summarize the tumor-suppressive functions of YAP/TAZ in different contexts. Based on these findings, we will further discuss the clinical implications of YAP/TAZ-based tumor targeted therapy and potential future directions. Graphical Abstract

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YAP1 and PRDM14 converge to promote cell survival and tumorigenesis

Cited by 12 publications

References 79 publications

SRSF3/AMOTL1 Splicing Axis Promotes the Tumorigenesis of Nasopharyngeal Carcinoma through Regulating the Nucleus Translocation of YAP1

SRSF3/AMOTL1 Splicing Axis Promotes the Tumorigenesis of Nasopharyngeal Carcinoma through Regulating the Nucleus Translocation of YAP1

SRSF3/AMOTL1 splicing axis promotes the tumorigenesis of nasopharyngeal carcinoma through regulating the nucleus translocation of YAP1

New insights into the ambivalent role of YAP/TAZ in human cancers

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