Sensitisation of Cancer Cells to MLN8237, an Aurora-A Inhibitor, by YAP/TAZ Inactivation

Oku, Yusuke; Nishiya, Naoyuki; Sugiyama, S.; Sato, Hirosuke; Uehara, Yoshimasa

doi:10.21873/anticanres.12617

Cited by 8 publications

(5 citation statements)

References 15 publications

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“…Several reports have supported this observed anti-proliferative activity of FLV against different cancer cells-for example, against pancreas [49], breast [50], glial [51], and colorectal [52] cancer cells. FLV has been shown to decrease resistance of melanoma [53], breast, and ovarian cells [54]. Further, FLV has shown strong growth-inhibitory and anti-metastatic effects on hepatocellular carcinoma cells [18,55].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells

Al-Wahaibi

Al-Saleem

Ahmed

et al. 2020

IJMS

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Accumulating evidence indicates that statins reduce the risk of different cancers and inhibit the proliferation of liver cancer cells. This study aims to explore whether the electrostatic conjugation of optimized fluvastatin (FLV) to human immunodeficiency virus type 1 (HIV-1) trans-activator transcription peptide (TAT) would enhance the anti-proliferative activity against HepG2 cells. FLV–TAT conjugation was optimized to achieve the lowest size with highest zeta potential. Nine formulae were constructed, using a factorial design with three factors—FLV concentration, TAT concentration, and pH of the medium—while the responses were zeta potential and size. The optimized formula showed a particle size of 199.24 nm and 29.14 mV zeta potential. Data indicates that conjugation of FLV to TAT (optimized formula) significantly enhances anti-proliferative activity and uptake by HepG2 cells when compared to raw FLV. Flow cytometry showed significant accumulation of cells in the pre-G phase, which highlights higher apoptotic activity. Annexin V staining indicated a significant increase in total cell death in early and late apoptosis. This was confirmed by significantly elevated caspase 3 in cells exposed to FLV–TAT preparation. In conclusion, the FLV–TAT optimized formula exhibited improved anti-proliferative action against HepG2. This is partially attributed to the enhanced apoptotic effects and cellular uptake of FLV.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells

Al-Wahaibi

Al-Saleem

Ahmed

et al. 2020

IJMS

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“…Other targeted therapies with resistance mechanisms associated with Hippo signaling include mTOR, TBK/IGF1R, imatinib, CDK4/6, WEE1 and Aurora-A inhibitors [38,[67][68][69][70][71]. Taken together, these studies provide concrete evidence for the involvement of Hippo-YAP/TAZ signaling in development of resistance to targeted therapies across multiple malignancies.…”

Section: Yap/taz Signaling and Resistance To Targeted Therapymentioning

confidence: 83%

YAP/TAZ Signaling and Resistance to Cancer Therapy

2019

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Drug resistance is a major challenge in cancer treatment. Emerging evidence indicates that deregulation of YAP/TAZ signaling may be a major mechanism of intrinsic and acquired resistance to various targeted and chemotherapies. Moreover, YAP/TAZ-mediated expression of PD-L1 and multiple cytokines is pivotal for tumor immune evasion. While direct inhibitors of YAP/TAZ are still under development, FDA-approved drugs that indirectly block YAP/TAZ activation or critical downstream targets of YAP/TAZ have shown promise in the clinic in reducing therapy resistance. Finally, BET inhibitors, which reportedly block YAP/TAZ-mediated transcription, present another potential venue to overcome YAP/TAZ-induced drug resistance.

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“…In addition, several studies proved that the YAP gene is amplified in cervical, ovarian, and fallopian tube cancers [30,31]. Moreover, silencing the expression of YAP gene by shRNA [18,32,33] or siRNA [15,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48] could induce apoptosis (Table 1). Consistent with this finding, overexpressing YAP significantly inhibited apoptosis of liver [38,49,50], pancreas [39], colorectal cancer [15,51], and lung cancer cells [52].…”

Section: The Anti-apoptotic Function Of Yapmentioning

confidence: 99%

The Ambivalent Function of YAP in Apoptosis and Cancer

Zhang

Abdelrahman

Vollmar

et al. 2018

IJMS

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Yes-associated protein, a core regulator of the Hippo-YAP signaling pathway, plays a vital role in inhibiting apoptosis. Thus, several studies and reviews suggest that yes-associated protein is a good target for treating cancer. Unfortunately, more and more evidence demonstrates that this protein is also an essential contributor of p73-mediated apoptosis. This questions the concept that yes-associated protein is always a good target for developing novel anti-cancer drugs. Thus, the aim of this review was to evaluate the clinical relevance of yes-associated protein for cancer pathophysiology. This review also summarized the molecules, processes and drugs, which regulate Hippo-YAP signaling and discusses their effect on apoptosis. In addition, issues are defined, which should be addressed in the future in order to provide a solid basis for targeting the Hippo-YAP signaling pathway in clinical trials.

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Sensitisation of Cancer Cells to MLN8237, an Aurora-A Inhibitor, by YAP/TAZ Inactivation

Abstract: A combination of MLN8237 and small-molecule agents inactivating YAP/TAZ, such as statins, could be a novel therapeutic strategy for YAP/TAZ-dependent cancer.

Cited by 8 publications

References 15 publications

RETRACTED: Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells

RETRACTED: Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells

YAP/TAZ Signaling and Resistance to Cancer Therapy

The Ambivalent Function of YAP in Apoptosis and Cancer

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