Related Experiment Video

Updated: Aug 9, 2026

Tumorsphere Derivation and Treatment from Primary Tumor Cells Isolated from Mouse Rhabdomyosarcomas
09:21

Tumorsphere Derivation and Treatment from Primary Tumor Cells Isolated from Mouse Rhabdomyosarcomas

Published on: September 13, 2019

Nuclear localized p70S6K maintain cancer stem-like properties by modulating RPA3 activity in osteosarcoma

Jing Zhou1, Bo Li2, Qi Gao2

  • 1Hubei Provincial Key Laboratory of Occurrence and Intervention of Kidney Diseases, Hubei Provincial Engineering Research Center of Immunotherapy Drugs for Renal Tumors, Faculty of Medicine, Collaborative Technology of Advanced Material Manufacturing and Solid Waste Recycling Hubei Engineering Research Center, School of Materials Science & Engineering, Hubei Polytechnic University, Huangshi, China; State Key Laboratory of Biocatalysis and Enzyme Engineering, Stem Cells and Tissue Engineering Manufacture Center, School of Life Sciences, Hubei University, Wuhan, China.

Cellular Signalling
|August 7, 2026
PubMed

Insights

Nuclear p70S6K interacts with RPA3 to drive cancer stem cell properties in osteosarcoma, offering a new therapeutic target. Blocking this pathway suppresses tumor growth, potentially improving osteosarcoma treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Stem Cell Research

Background:

  • Cancer stem-like cells (CSCs) drive therapeutic failure and chemoresistance in osteosarcoma.
  • Nuclear p70 ribosomal protein S6 kinase (p70S6K) is linked to poor prognosis, but its role in cancer development is understudied.
  • Replication protein A3 (RPA3) is highly expressed in osteosarcoma CSCs.

Purpose of the Study:

  • To investigate the novel nuclear function of p70S6K in osteosarcoma development.
  • To elucidate the mechanism by which nuclear p70S6K promotes CSC properties.
  • To evaluate the therapeutic potential of targeting the nuclear p70S6K-RPA3 axis.

Main Methods:

  • Single-cell transcriptomics to identify RPA3 expression in osteosarcoma CSCs.
  • Biochemical assays to study the interaction between p70S6K and RPA3.
  • Pharmacological inhibition of the p70S6K-RPA axis in osteosarcoma models.

Main Results:

  • Nuclear p70S6K physically interacts with RPA3, modulating its single-strand DNA-binding activity.
  • This interaction drives the acquisition and maintenance of CSC properties in osteosarcoma.
  • Pharmacological inhibition of the p70S6K-RPA axis significantly suppresses osteosarcoma tumor growth.

Conclusions:

  • This study reveals a novel nuclear function of p70S6K in promoting CSC maintenance via RPA3.
  • The nuclear p70S6K-RPA3 pathway is a critical driver of osteosarcoma progression.
  • Targeting the nuclear p70S6K-RPA3 axis presents a promising CSC-based therapeutic strategy for osteosarcoma.
Keywords:
Nuclear p70S6KOsteosarcomaRPA3cancer stem cell

More Related Videos

Establishment of Cancer Stem Cell Cultures from Human Conventional Osteosarcoma09:25

Establishment of Cancer Stem Cell Cultures from Human Conventional Osteosarcoma

Published on: October 14, 2016

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...
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...
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
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...