Related Experiment Video

Updated: Jan 3, 2026

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

9.1K

Causative role of PDLIM2 epigenetic repression in lung cancer and therapeutic resistance

Fan Sun1,2, Liwen Li1,2, Pengrong Yan1,2,3

  • 1UPMC Hillman Cancer Center, Pittsburgh, PA, 15213, USA.

Nature Communications
|November 24, 2019
PubMed

Insights

This study identifies PDLIM2 as a tumor suppressor crucial for lung cancer treatment. Restoring PDLIM2 enhances responses to immunotherapy and chemotherapy, offering new combination therapy strategies.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Most cancers exhibit resistance to current therapies like anti-PD-1/PD-L1 and chemotherapy.
  • Tumor suppressor PDLIM2 is epigenetically repressed in lung cancer, correlating with poor prognosis and therapeutic resistance.

Purpose of the Study:

  • To identify novel therapeutic targets for overcoming cancer treatment resistance.
  • To investigate the role of PDLIM2 in lung cancer development and response to therapy.

Main Methods:

  • Analysis of PDLIM2 epigenetic status in human lung cancer.
  • Generation of global and lung epithelial-specific PDLIM2-deficient mouse models.
  • Evaluation of PDLIM2 restoration and combination therapies (anti-PD-1, chemotherapy, epigenetic drugs) in preclinical models.

Main Results:

  • PDLIM2 deficiency in mice led to increased lung cancer, chemoresistance, and resistance to anti-PD-1 and epigenetic drugs.
  • PDLIM2 restoration or ectopic expression demonstrated antitumor activity and synergized with anti-PD-1 and chemotherapy, achieving complete remission in most lung cancers.
  • PDLIM2 represses NF-κB/RelA and STAT3, enhancing antigen presentation and T-cell activation while reducing multidrug resistance genes.

Conclusions:

  • PDLIM2 is a critical tumor suppressor for lung cancer therapeutic responses.
  • Restoring PDLIM2 function or using combination therapies involving PDLIM2 agonists represents a promising strategy for treating lung cancer.
  • PDLIM2-independent PD-L1 induction by drugs also contributes to synergistic effects with anti-PD-1 therapy.

More Related Videos

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

8.3K
Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression06:03

Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression

Published on: January 19, 2019

18.0K

Related Concept Videos

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...
5.0K
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.3K
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
3.7K
Genomic Imprinting and Inheritance02:30

Genomic Imprinting and Inheritance

Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
36.6K
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...
3.6K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.6K