Evidence map›Paper›PMID 35290241›Full record

ArticleThe Journal of clinical investigation2022

Combinatorial targeting of Hippo-STRIPAK and PARP elicits synthetic lethality in gastrointestinal cancers.

Liwei An, Zhifa Cao, Pingping Nie, Hui Zhang, Zhenzhu Tong, Fan Chen, Yang Tang, Yi Han, Wenjia Wang, Zhangting Zhao and 9 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 26 citations in OpenAlex.

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  20. Biomaterial-enabled therapeutic modulation of cGAS-STING signaling for enhancing antitumor immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 7 institutions in 1 country.

Liwei AnDepartment of Medical Ultrasound, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China.
Zhifa CaoState Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Pingping NieState Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Hui ZhangState Key Laboratory of Genetic Engineering, Zhongshan Hospital, School of Life Sciences, Fudan University, Shanghai, China.
Zhenzhu TongState Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Fan ChenState Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Yang TangDepartment of Medical Ultrasound, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China.
Yi HanDepartment of Medical Ultrasound, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China.
Wenjia WangState Key Laboratory of Genetic Engineering, Zhongshan Hospital, School of Life Sciences, Fudan University, Shanghai, China.
Zhangting ZhaoState Key Laboratory of Genetic Engineering, Zhongshan Hospital, School of Life Sciences, Fudan University, Shanghai, China.
Qingya ZhaoDepartment of Laboratory Animal Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yuqin YangDepartment of Laboratory Animal Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yuanzhi XuDepartment of Stomatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Gemin FangInstitutes of Physical Science and Information Technology, Anhui University, Hefei, China.
Lei ShiDepartment of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, China.
Huixiong XuDepartment of Medical Ultrasound, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China.
Haiqing MaDepartment of Oncology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Shi JiaoState Key Laboratory of Genetic Engineering, Zhongshan Hospital, School of Life Sciences, Fudan University, Shanghai, China.
Zhaocai ZhouState Key Laboratory of Genetic Engineering, Zhongshan Hospital, School of Life Sciences, Fudan University, Shanghai, China.
Fudan University · CNTongji University · CNCenter for Excellence in Molecular Cell Science · CNShanghai Jiao Tong University · CNAnhui University · CNGuangdong Academy of Medical Sciences · CNTianjin Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The striatin-interacting phosphatase and kinase (STRIPAK) complexes integrate extracellular stimuli that result in intracellular activities. Previously, we discovered that STRIPAK is a key machinery responsible for loss of the Hippo tumor suppressor signal in cancer. Here, we identified the Hippo-STRIPAK complex as an essential player in the control of DNA double-stranded break (DSB) repair and genomic stability. Specifically, we found that the mammalian STE20-like protein kinases 1 and 2 (MST1/2), independent of classical Hippo signaling, directly phosphorylated zinc finger MYND type-containing 8 (ZMYND8) and hence resulted in the suppression of DNA repair in the nucleus. In response to genotoxic stress, the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway was determined to relay nuclear DNA damage signals to the dynamic assembly of Hippo-STRIPAK via TANK-binding kinase 1-induced (TBK1-induced) structural stabilization of the suppressor of IKBKE 1- sarcolemma membrane-associated protein (SIKE1-SLMAP) arm. As such, we found that STRIPAK-mediated MST1/2 inactivation increased the DSB repair capacity of cancer cells and endowed these cells with resistance to radio- and chemotherapy and poly(ADP-ribose)polymerase (PARP) inhibition. Importantly, targeting the STRIPAK assembly with each of 3 distinct peptide inhibitors efficiently recovered the kinase activity of MST1/2 to suppress DNA repair and resensitize cancer cells to PARP inhibitors in both animal- and patient-derived tumor models. Overall, our findings not only uncover what we believe to be a previously unrecognized role for STRIPAK in modulating DSB repair but also provide translational implications of cotargeting STRIPAK and PARP for a new type of synthetic lethality anticancer therapy.

Indexed as

Gastrointestinal NeoplasmsPhosphoric Monoester HydrolasesAnimalsHumansMammalsPoly(ADP-ribose) Polymerase InhibitorsSignal TransductionSynthetic Lethal MutationsTranscription FactorsPhosphoric Monoester HydrolasesPoly(ADP-ribose) Polymerase InhibitorsTranscription FactorsCell BiologyDrug therapyGastric cancerGastroenterologyMolecular biology

Identifiers

PMID35290241
PMCPMC9057599
OpenAlexW4220672470

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.