Related Experiment Video

Updated: Feb 20, 2026

Mimicking and Manipulating Pancreatic Acinar-to-Ductal Metaplasia in 3-dimensional Cell Culture
08:16

Mimicking and Manipulating Pancreatic Acinar-to-Ductal Metaplasia in 3-dimensional Cell Culture

Published on: February 11, 2019

9.4K

SOX9 activity is induced by oncogenic Kras to affect MDC1 and MCMs expression in pancreatic cancer

H Zhou1,2, Y Qin3,4, S Ji3,4

  • 1Department of Molecular and Cellular Oncology, the University of Texas MD Anderson Cancer Centre, Houston, TX, USA.

Oncogene
|October 24, 2017
PubMed

Insights

Oncogenic Kras activates SOX9 in pancreatic cancer cells, promoting proliferation and influencing key genes like MDC1, which may indicate less tumor invasion.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • SRY (sex determining region Y)-box 9 (SOX9) is crucial for oncogenic Kras-driven pancreatic ductal adenocarcinoma (PDAC) development.
  • The precise mechanisms by which oncogenic Kras influences SOX9 activity and the genes associated with SOX9 in PDAC remain largely unelucidated.

Purpose of the Study:

  • To investigate the mechanistic link between SOX9 and oncogenic Kras in PDAC.
  • To elucidate the biological functions of SOX9 in pancreatic cells.
  • To identify SOX9-related genes and assess their clinical significance in PDAC patients.

Main Methods:

  • Analysis of SOX9 expression (mRNA, protein, phosphorylation) in human pancreatic ductal progenitor cells (HPNE) and pancreatic ductal cells (HPDE) with oncogenic Kras.
  • Assessment of SOX9 nuclear translocation and transcriptional activity.
  • Investigation of the TAK1/IκBα/NF-κB pathway's role in Kras-mediated SOX9 induction.
  • Evaluation of SOX9's effect on cell proliferation and correlation with minichromosome maintenance complex components (MCMs) and mediator of DNA damage checkpoint 1 (MDC1).

Main Results:

  • Oncogenic Kras significantly upregulates SOX9 expression and promotes its nuclear translocation and transcriptional activity in pancreatic ductal cells.
  • The Kras/TAK1/IκBα/NF-κB pathway is involved in SOX9 induction, with SOX9 reciprocally enhancing NF-κB activation, indicating a positive feedback loop.
  • SOX9 promotes the proliferation of HPNE and PDAC cells and correlates with MCMs and MDC1 expression.
  • Overexpression of MDC1 is associated with reduced perineural and lymph node invasion and earlier TNM stage in PDAC patients.

Conclusions:

  • Oncogenic Kras induces constitutive SOX9 activation in pancreatic ductal cells via the Kras/TAK1/IκBα/NF-κB pathway and a SOX9-NF-κB positive feedback loop.
  • SOX9 contributes to PDAC progression by accelerating cell proliferation and influencing MCMs and MDC1 expression.
  • MDC1 shows potential as a prognostic marker, negatively correlating with PDAC invasion and metastasis.

More Related Videos

Dissection of the Mouse Pancreas for Histological Analysis and Metabolic Profiling08:21

Dissection of the Mouse Pancreas for Histological Analysis and Metabolic Profiling

Published on: August 19, 2017

40.1K
Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line06:24

Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line

Published on: April 11, 2025

956

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...
4.9K
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...
5.3K
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...
5.7K
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...
5.8K