TRIM27 promotes the Warburg effect and glioblastoma progression via inhibiting the LKB1/AMPK/mTOR axis

Juexian Xiao1, Haitao Luo1, Shikai Gui1

  • 1Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University Nanchang 330006, Jiangxi, China.

Insights

Tripartite motif 27 (TRIM27) promotes glioblastoma growth by enhancing the Warburg effect and inhibiting the LKB1/AMPK/mTOR pathway. TRIM27 may serve as a diagnostic and therapeutic target for glioblastoma patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Altered protein ubiquitination is a hallmark of cancer.
  • Tripartite motif (TRIM) E3 ubiquitin ligases are implicated in tumor development, growth, and metastasis.
  • TRIM27 is a potential tumor promoter, but its role in glioblastoma (GBM) is largely unknown.

Purpose of the Study:

  • To investigate the biological functions and clinical relevance of TRIM27 in glioblastoma.
  • To elucidate the molecular mechanisms underlying TRIM27's role in GBM pathogenesis.

Main Methods:

  • Analysis of TRIM27 expression in GBM tissues and cell lines.
  • In vitro and in vivo functional assays to assess the impact of TRIM27 deletion on GBM cell growth.
  • Investigation of TRIM27's effect on the Warburg effect and the LKB1/AMPK/mTOR signaling pathway.
  • Co-immunoprecipitation assays to determine the interaction between TRIM27 and LKB1.

Main Results:

  • TRIM27 expression is elevated in GBM tissues and cell lines.
  • TRIM27 deletion significantly inhibits GBM cell proliferation in vitro and tumor growth in vivo.
  • TRIM27 promotes GBM growth by enhancing the Warburg effect via inactivation of the LKB1/AMPK/mTOR pathway.
  • TRIM27 directly binds to LKB1, promoting its ubiquitination and degradation.

Conclusions:

  • TRIM27 plays a crucial oncogenic role in glioblastoma.
  • TRIM27 contributes to GBM pathogenesis by inhibiting the LKB1/AMPK/mTOR axis, thereby enhancing the Warburg effect.
  • TRIM27 represents a potential diagnostic and therapeutic biomarker for glioblastoma.

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.5K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.1K