Related Experiment Video

Updated: Jun 18, 2025

LINE-1 Methylation Analysis in Mesenchymal Stem Cells Treated with Osteosarcoma-Derived Extracellular Vesicles
12:18

LINE-1 Methylation Analysis in Mesenchymal Stem Cells Treated with Osteosarcoma-Derived Extracellular Vesicles

Published on: February 1, 2020

5.7K

FOXM1 mediates methotrexate resistance in osteosarcoma cells by promoting autophagy

Luoyang Wang1, Dongchang Zhai2, Lei Tang2

  • 1Department of Immunology, School of Basic Medicine, Qingdao University, Qingdao 266071, China.

Acta Biochimica Et Biophysica Sinica
|August 1, 2024
PubMed

Insights

Transcription factor FOXM1 drives methotrexate resistance in osteosarcoma by enhancing autophagy. Targeting FOXM1 or autophagy may improve chemotherapy outcomes for this bone cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Osteosarcoma (OS) is a primary bone cancer predominantly affecting adolescents and the elderly.
  • Current OS treatment relies heavily on chemotherapy, but drug resistance significantly hinders therapeutic success.
  • The transcription factor FOXM1 is implicated in various cancer processes, including drug resistance, but its role in methotrexate resistance in OS is unexplored.

Purpose of the Study:

  • To investigate the role of FOXM1 in methotrexate (MTX) resistance in osteosarcoma.
  • To elucidate the underlying molecular mechanisms of FOXM1-mediated MTX resistance.

Main Methods:

  • Assessed FOXM1 expression in OS tissues and MTX-resistant cells.
  • Investigated the effect of FOXM1 overexpression and silencing on MTX sensitivity.
  • Examined the role of autophagy, specifically the HMMR/ATG7 pathway, in FOXM1-induced MTX resistance.

Main Results:

  • FOXM1 was highly expressed in OS tissues and MTX-resistant cells, correlating with MTX resistance.
  • FOXM1 overexpression promoted MTX resistance by enhancing autophagy in an HMMR/ATG7-dependent manner.
  • Silencing FOXM1 or inhibiting autophagy effectively reversed MTX resistance in OS cells.

Conclusions:

  • FOXM1 plays a critical role in conferring MTX resistance in osteosarcoma.
  • FOXM1 enhances MTX resistance through an autophagy-dependent pathway involving HMMR/ATG7.
  • Targeting FOXM1 or the autophagy pathway presents a potential therapeutic strategy to overcome MTX resistance in OS.
Keywords:
FOXM1drug resistancemethotrexateosteosarcoma

More Related Videos

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer09:40

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

2.6K
A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells11:15

A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells

Published on: May 6, 2018

10.2K

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
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
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
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
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.2K