The deubiquitinase USP16 functions as an oncogenic factor in K-RAS-driven lung tumorigenesis

doi:10.1038/s41388-021-01964-6

. 2021 Sep;40(36):5482-5494.

doi: 10.1038/s41388-021-01964-6. Epub 2021 Jul 22.

The deubiquitinase USP16 functions as an oncogenic factor in K-RAS-driven lung tumorigenesis

Guiqin Xu^#¹, Zhaojuan Yang^#¹, Yizong Ding^#², Yun Liu¹, Li Zhang¹, Boshi Wang¹, Ming Tang¹, Tiantian Jing¹, Kun Jiao³, Xiaoli Xu³, Zehong Chen¹, Lvzhu Xiang¹, Chen Xu¹, Yujie Fu², Xiaojing Zhao², Weilin Jin⁴, Yongzhong Liu⁵

Affiliations

¹ State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Thoracic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, China.
⁴ Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou, People's Republic of China.
⁵ State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. liuyzg@shsci.org.

^# Contributed equally.

PMID: 34294846
DOI: 10.1038/s41388-021-01964-6

The deubiquitinase USP16 functions as an oncogenic factor in K-RAS-driven lung tumorigenesis

Guiqin Xu et al. Oncogene. 2021 Sep.

. 2021 Sep;40(36):5482-5494.

doi: 10.1038/s41388-021-01964-6. Epub 2021 Jul 22.

Authors

Affiliations

¹ State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Thoracic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, China.
⁴ Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou, People's Republic of China.
⁵ State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. liuyzg@shsci.org.

^# Contributed equally.

PMID: 34294846
DOI: 10.1038/s41388-021-01964-6

Abstract

K-RAS mutation and molecular alterations of its surrogates function essentially in lung tumorigenesis and malignant progression. However, it remains elusive how tumor-promoting and deleterious events downstream of K-RAS signaling are coordinated in lung tumorigenesis. Here, we show that USP16, a deubiquitinase involved in various biological processes, functions as a promoter for the development of K-RAS-driven lung tumor. Usp16 deletion significantly attenuates K-ras^G12D-mutation-induced lung tumorigenesis in mice. USP16 upregulation upon RAS activation averts reactive oxygen species (ROS)-induced p38 activation that would otherwise detrimentally influence the survival and proliferation of tumor cells. In addition, USP16 interacts with and deubiquitinates JAK1, and thereby promoting lung tumor growth by augmenting JAK1 signaling. Therefore, our results reveal that USP16 functions critically in the K-RAS-driven lung tumorigenesis through modulating the strength of p38 and JAK1 signaling.

PubMed Disclaimer

Cited by

USP10 promotes migration and cisplatin resistance in esophageal squamous cell carcinoma cells.
Hou S, Zhao T, Deng B, Li C, Li W, Huang H, Hang Q. Hou S, et al. Med Oncol. 2023 Dec 27;41(1):33. doi: 10.1007/s12032-023-02272-7. Med Oncol. 2023. PMID: 38150085
A SIX1 degradation inducer blocks excessive proliferation of prostate cancer.
Liao Y, Sun W, Shao Z, Liu Y, Zhong X, Deng Y, Liu F, Huang H, Liu J. Liao Y, et al. Int J Biol Sci. 2022 Mar 14;18(6):2439-2451. doi: 10.7150/ijbs.67873. eCollection 2022. Int J Biol Sci. 2022. PMID: 35414775 Free PMC article.
Critical role of lncEPAT in coupling dysregulated EGFR pathway and histone H2A deubiquitination during glioblastoma tumorigenesis.
Li L, Zhou A, Wei Y, Liu F, Li P, Fang R, Ma L, Zhang S, Wang L, Liu J, Richard HT, Chen Y, Wang H, Huang S. Li L, et al. Sci Adv. 2022 Oct 7;8(40):eabn2571. doi: 10.1126/sciadv.abn2571. Epub 2022 Oct 5. Sci Adv. 2022. PMID: 36197973 Free PMC article.
Roles of deubiquitinases in urologic cancers (Review).
Wu L, Wang J, Chai L, Chen J, Jin X. Wu L, et al. Oncol Lett. 2024 Oct 14;28(6):609. doi: 10.3892/ol.2024.14743. eCollection 2024 Dec. Oncol Lett. 2024. PMID: 39525605 Free PMC article. Review.
USP24 promotes autophagy-dependent ferroptosis in hepatocellular carcinoma by reducing the K48-linked ubiquitination of Beclin1.
Cao J, Wu S, Zhao S, Wang L, Wu Y, Song L, Sun C, Liu Y, Liu Z, Zhu R, Liang R, Wang W, Sun Y. Cao J, et al. Commun Biol. 2024 Oct 8;7(1):1279. doi: 10.1038/s42003-024-06999-5. Commun Biol. 2024. PMID: 39379617 Free PMC article.

See all "Cited by" articles

References

1. Ali SA, Justilien V, Jamieson L, Murray NR, Fields AP. Protein kinase ciota drives a NOTCH3-dependent stem-like phenotype in mutant KRAS lung adenocarcinoma. Cancer Cell. 2016;29:367–78. - PubMed - PMC - DOI
1. Gwinn DM, Lee AG, Briones-Martin-Del-Campo M, Conn CS, Simpson DR, Scott AI, et al. Oncogenic KRAS regulates amino acid homeostasis and asparagine biosynthesis via ATF4 and alters sensitivity to L-asparaginase. Cancer Cell. 2018;33:91–107 e106. - PubMed - PMC - DOI
1. Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene. 2007;26:3279–90. - PubMed - DOI
1. Kennedy NJ, Cellurale C, Davis RJ. A radical role for p38 MAPK in tumor initiation. Cancer Cell. 2007;11:101–3. - PubMed - DOI
1. Sun P, Yoshizuka N, New L, Moser BA, Li Y, Liao R, et al. PRAK is essential for ras-induced senescence and tumor suppression. Cell. 2007;128:295–308. - PubMed - DOI

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Nature Publishing Group
Medical
- MedlinePlus Health Information
Molecular Biology Databases
- Mouse Genome Informatics (MGI)
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

[1] Ali SA, Justilien V, Jamieson L, Murray NR, Fields AP. Protein kinase ciota drives a NOTCH3-dependent stem-like phenotype in mutant KRAS lung adenocarcinoma. Cancer Cell. 2016;29:367–78. - PubMed - PMC - DOI

[2] Ali SA, Justilien V, Jamieson L, Murray NR, Fields AP. Protein kinase ciota drives a NOTCH3-dependent stem-like phenotype in mutant KRAS lung adenocarcinoma. Cancer Cell. 2016;29:367–78. - PubMed - PMC - DOI

[3] Gwinn DM, Lee AG, Briones-Martin-Del-Campo M, Conn CS, Simpson DR, Scott AI, et al. Oncogenic KRAS regulates amino acid homeostasis and asparagine biosynthesis via ATF4 and alters sensitivity to L-asparaginase. Cancer Cell. 2018;33:91–107 e106. - PubMed - PMC - DOI

[4] Gwinn DM, Lee AG, Briones-Martin-Del-Campo M, Conn CS, Simpson DR, Scott AI, et al. Oncogenic KRAS regulates amino acid homeostasis and asparagine biosynthesis via ATF4 and alters sensitivity to L-asparaginase. Cancer Cell. 2018;33:91–107 e106. - PubMed - PMC - DOI

[5] Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene. 2007;26:3279–90. - PubMed - DOI

[6] Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene. 2007;26:3279–90. - PubMed - DOI

[7] Kennedy NJ, Cellurale C, Davis RJ. A radical role for p38 MAPK in tumor initiation. Cancer Cell. 2007;11:101–3. - PubMed - DOI

[8] Kennedy NJ, Cellurale C, Davis RJ. A radical role for p38 MAPK in tumor initiation. Cancer Cell. 2007;11:101–3. - PubMed - DOI

[9] Sun P, Yoshizuka N, New L, Moser BA, Li Y, Liao R, et al. PRAK is essential for ras-induced senescence and tumor suppression. Cell. 2007;128:295–308. - PubMed - DOI

[10] Sun P, Yoshizuka N, New L, Moser BA, Li Y, Liao R, et al. PRAK is essential for ras-induced senescence and tumor suppression. Cell. 2007;128:295–308. - PubMed - DOI

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

The deubiquitinase USP16 functions as an oncogenic factor in K-RAS-driven lung tumorigenesis

Affiliations

The deubiquitinase USP16 functions as an oncogenic factor in K-RAS-driven lung tumorigenesis

Authors

Affiliations

Abstract

Similar articles

Cited by

References

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Molecular Biology Databases

Research Materials

Miscellaneous

Abstract

Similar articles

Cited by

References

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources

Medical

Molecular Biology Databases

Research Materials

Miscellaneous