2. Academic Validation
  3. PKMYT1 inhibits lung adenocarcinoma progression by abrogating AKT1 activity

PKMYT1 inhibits lung adenocarcinoma progression by abrogating AKT1 activity

  • Cell Oncol (Dordr). 2022 Nov 9. doi: 10.1007/s13402-022-00744-y.
Shuang Wang # 1,  Ximeng Liu # 1,  Ting Zhou 2,  Jinling Li 1,  Ying Lin 2,  Anni Zhou 3,  Jiamin Huang 1,  Jingjing Zhao 4,  Junchao Cai 2,  Xiuyu Cai 5,  Yongbo Huang 6,  Xu Li 7
Affiliations

Affiliations

  • 1 Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.
  • 2 Department of Immunology, Sun Yat-Sen University Zhongshan School of Medicine, Guangzhou, 510080, China.
  • 3 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.
  • 4 Department of Cardiac Surgery Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
  • 5 Department of General Internal Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
  • 6 State Key Laboratory of Respiratory Diseases and Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510060, China. [email protected].
  • 7 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China. [email protected].
  • # Contributed equally.
PMID: 36350496 DOI: 10.1007/s13402-022-00744-y
Abstract

Purpose: Akt hyperactivation drives malignant phenotypes in lung Cancer via promoting tumor cell proliferation and survival. However, the relationship between dysregulation of cell cycle progression and Akt1 kinase activity is still not clear.

Methods: Following the expression level of PKMYT1 in lung Cancer, we performed cell proliferation, migration, invasion, and xenograft assays to determine the function of PKMYT1. We used RNA-seq to explore the anti-tumor mechanism of PKMYT1 and examined the effect of PKMYT1 on Akt1 activity.

Results: In this study, we report that PKMYT1 is downregulated in lung adenocarcinoma (LUAD) tissues and its low expression predicts a poor prognosis in LUAD patients. PKMYT1 exerts potent tumor-suppressive functions in LUAD cells by inhibiting Akt1 activation and thereby repressing cell cycle progression, which depends on its tyrosine and threonine protein kinase activity. Interestingly, PKMYT1 could directly bind Akt1 to abrogate Akt1 activation. Moreover, silencing Akt1 and inhibitors targeting the Akt pathway effectively reverse the promoting effects of PKMYT1 knockdown on proliferation, migration and invasion of LUAD cells.

Conclusion: This work reveals the anti-tumor effect of PKMYT1 in LUAD and provides evidence to clarify the dual roles of PKMYT1 in tumor progression. Moreover, our findings broaden the current understandings on Akt1 activation and identify PKMYT1 as a potential negative regulator of Akt1 kinase activity, providing further insights into targeting the Akt pathway in LUAD.

Keywords

AKT1; Cell cycle; Lung adenocarcinoma; PKMYT1.

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