2. Academic Validation
  3. Humanin activates integrin αV-TGFβ axis and leads to glioblastoma progression

Humanin activates integrin αV-TGFβ axis and leads to glioblastoma progression

  • Cell Death Dis. 2024 Jun 28;15(6):464. doi: 10.1038/s41419-024-06790-8.
Cuong P Ha # 1 2 3,  Tuyen N M Hua # 1 2 3 4,  Vu T A Vo 1 2 3,  Jiyeon Om 1,  Sangwon Han 5,  Seung-Kuy Cha 2 3 6 7 8,  Kyu-Sang Park 9 10 11 12 13,  Yangsik Jeong 14 15 16 17 18
Affiliations

Affiliations

  • 1 Department of Biochemistry, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea.
  • 2 Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea.
  • 3 Mitohormesis Research Center, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea.
  • 4 Department of Pharmacology - Clinical Pharmacy, Faculty of Pharmacy, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam.
  • 5 Department of Ophthalmology, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea.
  • 6 Department of Physiology, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea.
  • 7 Institutes of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea.
  • 8 Mitochondrial Medicine, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea.
  • 9 Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea. qsang@yonsei.ac.kr.
  • 10 Mitohormesis Research Center, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea. qsang@yonsei.ac.kr.
  • 11 Department of Physiology, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea. qsang@yonsei.ac.kr.
  • 12 Institutes of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea. qsang@yonsei.ac.kr.
  • 13 Mitochondrial Medicine, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea. qsang@yonsei.ac.kr.
  • 14 Department of Biochemistry, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea. yjeong@yonsei.ac.kr.
  • 15 Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea. yjeong@yonsei.ac.kr.
  • 16 Mitohormesis Research Center, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea. yjeong@yonsei.ac.kr.
  • 17 Institutes of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea. yjeong@yonsei.ac.kr.
  • 18 Mitochondrial Medicine, Wonju College of Medicine, Yonsei University, Wonju, 26426, Republic of Korea. yjeong@yonsei.ac.kr.
  • # Contributed equally.
PMID: 38942749 DOI: 10.1038/s41419-024-06790-8
Abstract

The role of mitochondria Peptides in the spreading of glioblastoma remains poorly understood. In this study, we investigated the mechanism underlying intracranial glioblastoma progression. Our findings demonstrate that the mitochondria-derived peptide, humanin, plays a significant role in enhancing glioblastoma progression through the intratumoral activation of the Integrin alpha V (ITGAV)-TGF beta (TGFβ) signaling axis. In glioblastoma tissues, humanin showed a significant upregulation in the tumor area compared to the corresponding normal region. Utilizing multiple in vitro pharmacological and genetic approaches, we observed that humanin activates the ITGAV pathway, leading to cellular attachment and filopodia formation. This process aids the subsequent migration and invasion of attached glioblastoma cells through intracellular TGFβR signaling activation. In addition, our in vivo orthotopic glioblastoma model provides further support for the pro-tumoral function of humanin. We observed a correlation between poor survival and aggressive invasiveness in the humanin-treated group, with noticeable tumor protrusions and induced angiogenesis compared to the control. Intriguingly, the in vivo effect of humanin on glioblastoma was significantly reduced by the treatment of TGFBR1 inhibitor. To strengthen these findings, public database analysis revealed a significant association between genes in the ITGAV-TGFβR axis and poor prognosis in glioblastoma patients. These results collectively highlight humanin as a pro-tumoral factor, making it a promising biological target for treating glioblastoma.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-112842
    99.86%, Rac/Cdc42 抑制剂
    Ras; CDK
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