Related Experiment Video

Updated: Aug 6, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Downregulation of mTORC1 Signaling is Associated with Increased Sensitivity to Protein Synthesis Perturbations in

Didhiti Singha1, Debopriya Choudhury1, Meghna Mondal1

  • 1Department of Biomedical Science and Technology, School of Biological Sciences, Ramakrishna Mission Vivekananda Educational and Research Institute (RKMVERI), Kolkata 711202, India.

ACS Omega
|July 24, 2026
PubMed

Insights

Multiple myeloma cells are highly sensitive to disruptions in protein synthesis, with mTORC1 inhibition showing therapeutic potential. Targeting mTORC1 can overcome drug resistance in multiple myeloma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Protein synthesis is vital for multiple myeloma cell survival and proliferation.
  • Mammalian target of rapamycin complex 1 (mTORC1) signaling regulates protein synthesis via S6K1 and S6.
  • The sensitivity of multiple myeloma to protein synthesis stress and the therapeutic role of mTORC1 inhibition are not fully understood.

Purpose of the Study:

  • To investigate the sensitivity of multiple myeloma cells to protein synthesis perturbations.
  • To elucidate the role of S6K1 and S6 signaling in response to translational stress.
  • To evaluate the therapeutic potential of mTORC1 inhibition in multiple myeloma.

Main Methods:

  • Exposed multiple myeloma and non-myeloma cancer cell lines to protein synthesis perturbations.
  • Analyzed mTORC1 signaling (S6K1 and S6 activity) and global protein synthesis.
  • Assessed cellular responses (proliferation, apoptosis) and effects of mTORC1 inhibitor Torin1.
  • Compared sensitivity across different cancer types, including bortezomib-resistant cells.

Main Results:

  • Multiple myeloma cells showed heightened sensitivity to protein synthesis stress, with suppressed S6K1/S6 signaling and reduced protein synthesis.
  • This sensitivity led to decreased proliferation and increased apoptosis compared to other cancer cells.
  • mTORC1 inhibition with Torin1 significantly inhibited multiple myeloma cells, resensitized resistant cells, and restored bortezomib sensitivity in a resistant cell line.

Conclusions:

  • Established a mechanistic link between mTORC1 signaling, protein synthesis stress, and multiple myeloma.
  • Targeting mTORC1 enhances sensitivity to translational stress and overcomes drug resistance in multiple myeloma.
  • mTORC1 inhibition represents a potential therapeutic vulnerability for multiple myeloma treatment.

More Related Videos

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation09:37

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

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...
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...
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 rapamycin-insensitive companion...
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 daughter...
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...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...