Related Experiment Video

Updated: Apr 27, 2026

Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs
10:32

Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs

Published on: December 19, 2019

10.4K

Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer

Avnish Kapoor1, Wantong Yao1,2, Haoqiang Ying1,2

  • 1Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.

Cell
|June 24, 2014
PubMed

Insights

Pancreatic cancer (PDAC) tumors can become independent of KRAS mutations. Researchers found that Yap1 amplification drives tumor recurrence by activating cell cycle and DNA replication pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Activating KRAS mutations are common in pancreatic ductal adenocarcinoma (PDAC).
  • Sustained KRAS signaling is crucial for PDAC tumor maintenance.
  • Understanding KRAS-independent recurrence mechanisms is vital for effective PDAC treatment.

Purpose of the Study:

  • To investigate mechanisms of KRAS-independent PDAC recurrence.
  • To identify novel pathways driving tumor maintenance after loss of KRAS signaling.

Main Methods:

  • Utilized an inducible Kras(G12D)-driven mouse model of PDAC.
  • Analyzed relapsed tumors for genetic alterations and signaling pathway activation.
  • Performed functional studies on Yap1 and Tead2 in tumor maintenance.

Main Results:

  • Some PDAC tumors relapsed without Kras(G12D) expression or MAPK signaling.
  • Relapsed tumors acquired amplification and overexpression of Yap1.
  • Yap1/Tead2 complex, with E2F factors, drives Kras(G12D)-independent tumor maintenance via cell cycle and DNA replication pathways.

Conclusions:

  • Yap1/Tead2 signaling represents a novel escape mechanism from oncogenic KRAS addiction in PDAC.
  • This finding offers potential new therapeutic targets for overcoming PDAC treatment resistance.

More Related Videos

De Novo Generation of Somatic Stem Cells by YAP/TAZ13:05

De Novo Generation of Somatic Stem Cells by YAP/TAZ

Published on: May 7, 2018

11.3K
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.9K

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...
3.6K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.5K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
5.7K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.8K
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...
4.0K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.2K