Related Experiment Video

Updated: Nov 1, 2025

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

7.5K

Targeting therapy-resistant lung cancer stem cells via disruption of the AKT/TSPYL5/PTEN positive-feedback loop

In-Gyu Kim1,2, Jei-Ha Lee3, Seo-Yeon Kim3

  • 1Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Daejeon, South Korea. igkim@kaeri.re.kr.

Communications Biology
|June 24, 2021
PubMed

Insights

Testis-specific Y-like protein 5 (TSPYL5) regulates cancer stem cells in lung cancer. Inhibiting TSPYL5 phosphorylation offers a new therapeutic strategy to eliminate therapy-resistant cancer stem cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Cancer stem cells (CSCs) drive tumor progression and therapeutic resistance.
  • Targeting CSCs is crucial for effective cancer treatment, but practical strategies are limited.

Purpose of the Study:

  • To identify upstream regulators of CSC-associated genes in non-small cell lung cancer (NSCLC).
  • To evaluate testis-specific Y-like protein 5 (TSPYL5) as a potential therapeutic target for CSC elimination.

Main Methods:

  • Investigated TSPYL5 as a regulator of CSC markers ALDH1 and CD44 in NSCLC cells.
  • Examined the role of AKT-dependent phosphorylation and ubiquitination in TSPYL5 stabilization.
  • Analyzed TSPYL5's effect on PTEN transcription and PI3K signaling.

Main Results:

  • TSPYL5 acts as an upstream regulator of CSC-associated genes ALDH1 and CD44.
  • AKT-dependent phosphorylation of TSPYL5 at threonine-120 (TSPYL5-pT120) enhances its stability and nuclear translocation.
  • Nuclear TSPYL5 activates CSC genes and suppresses PTEN, creating a positive feedback loop with AKT/TSPYL5/PTEN signaling, maintaining CSC characteristics.

Conclusions:

  • TSPYL5-pT120 is a key driver of CSC-like properties in NSCLC.
  • Targeting TSPYL5-pT120 can disrupt the AKT/TSPYL5/PTEN signaling pathway.
  • TSPYL5 represents a promising therapeutic target for overcoming resistance in advanced cancers.

More Related Videos

Targeted and Selective Treatment of Pluripotent Stem Cell-derived Teratomas Using External Beam Radiation in a Small-animal Model05:08

Targeted and Selective Treatment of Pluripotent Stem Cell-derived Teratomas Using External Beam Radiation in a Small-animal Model

Published on: February 17, 2019

6.3K
Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies07:29

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies

Published on: June 20, 2015

19.8K

Related Concept Videos

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...
8.0K
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...
5.2K
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...
3.5K
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...
4.0K
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...
5.3K
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...
4.3K