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MASTL regulates EGFR signaling to impact pancreatic cancer progression

Iram Fatima1, Susmita Barman1, JayaPrakash Uppada2

  • 1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.

Oncogene
|July 31, 2021
PubMed

Insights

Greatwall kinase (MASTL) drives pancreatic cancer (PC) malignancy and therapy resistance by affecting EGFR stability. Targeting MASTL enhances Gemcitabine efficacy, offering a new strategy against pancreatic cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Pancreatic cancer (PC) is a leading cause of cancer mortality, characterized by significant therapy resistance.
  • Checkpoint inhibitors show promise in combination therapies, but novel targets are needed.
  • The role of Greatwall kinase (microtubule-associated serine/threonine-protein kinase-like (MASTL)) in PC is currently unknown.

Purpose of the Study:

  • To investigate the role of MASTL in pancreatic cancer progression and therapy resistance.
  • To elucidate the underlying mechanisms by which MASTL influences PC.
  • To evaluate MASTL as a potential therapeutic target for enhancing anti-PC therapies.

Main Methods:

  • Analysis of PC patient samples and murine models (Kras;PdxCre-KC and Kras;p53;PdxCre-KPC).
  • Loss and gain of function studies to assess MASTL's impact.
  • Investigation of MASTL's effect on epidermal growth factor receptor (EGFR) protein stability and signaling.
  • Evaluation of combinatorial therapy targeting MASTL with Gemcitabine.

Main Results:

  • MASTL plays a critical, previously undescribed role in promoting pancreatic cancer malignancy and therapy resistance.
  • MASTL promotes PC progression by modulating EGFR protein stability and downstream kinase signaling.
  • Combined inhibition of MASTL and Gemcitabine significantly enhances anti-cancer efficacy.

Conclusions:

  • MASTL is a key driver of pancreatic cancer progression and resistance to therapy.
  • Targeting MASTL represents a promising novel strategy to improve the sensitivity of pancreatic cancer to existing treatments like Gemcitabine.

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