Metabolic reprogramming driven by METTL1-mediated tRNA m7G modification promotes acquired anlotinib resistance in

Related Experiment Video

Updated: Jul 4, 2025

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

8.8K

Jie Chen1, Qimin Zhou2, Shuai Li3

  • 1Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China.

Translational Research : the Journal of Laboratory and Clinical Medicine
|January 27, 2024
PubMed

Insights

METTL1 promotes anlotinib resistance in oral squamous cell carcinoma (OSCC) by enhancing mRNA translation and oxidative phosphorylation. Targeting METTL1 or OXPHOS may overcome TKI resistance in OSCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Tyrosine kinase inhibitors (TKIs) like anlotinib are crucial for treating oral squamous cell carcinoma (OSCC).
  • Mechanisms of anlotinib resistance in OSCC are not fully understood.
  • Identifying resistance pathways is vital for improving patient outcomes.

Purpose of the Study:

  • To investigate the role of METTL1 in the development of anlotinib resistance in OSCC.
  • To elucidate the molecular mechanisms by which METTL1 contributes to anlotinib resistance.
  • To explore potential therapeutic strategies targeting METTL1-mediated resistance.

Main Methods:

  • Comparative analysis of METTL1 expression in anlotinib-sensitive and resistant OSCC cells.
  • In vitro and in vivo (transgenic mouse models) experiments to assess METTL1's role in resistance.
  • Investigation of METTL1's impact on mRNA translation and oxidative phosphorylation (OXPHOS) via m7G tRNA modification.
  • Bioenergetic profiling to analyze metabolic shifts.
  • Assessment of OXPHOS inhibition as a counter-resistance strategy.

Main Results:

  • METTL1 expression is significantly upregulated in anlotinib-resistant OSCC cells.
  • Elevated METTL1 promotes anlotinib resistance in both in vitro and in vivo models.
  • METTL1 enhances global mRNA translation and stimulates OXPHOS through m7G tRNA modification.
  • METTL1 drives a metabolic shift from glycolysis to OXPHOS in resistant cells.
  • Inhibiting OXPHOS reverses the effect of METTL1 on anlotinib resistance.

Conclusions:

  • METTL1 is a key mediator of anlotinib resistance in OSCC.
  • METTL1-driven m7G tRNA modification enhances translation and OXPHOS, conferring resistance.
  • Targeting METTL1 or OXPHOS presents a promising therapeutic approach to overcome anlotinib resistance in OSCC.
Keywords:
METTL1Mitochondrial metabolic reprogrammingTumor TKI resistancetRNA m7G modifications

More Related Videos

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

17.9K
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib09:38

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

8.0K

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
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...
3.6K
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
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.6K
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.6K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K