ROCK1 regulates glycolysis in pancreatic cancer via the c-MYC/PFKFB3 pathway

Shuyang Pang1, Yuting Shen1, Yanan Wang1

  • 1School of Life Science and Technology, China Pharmaceutical University, 639, Longmian Avenue, Nanjing, Jiangsu 211198, PR China.

Abstract

Insights

Rho-associated coiled coil-containing protein kinase 1 (ROCK1) promotes pancreatic cancer growth by enhancing glycolysis via the c-MYC/PFKFB3 pathway. Inhibiting ROCK1 may offer a new therapeutic strategy for pancreatic cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Dysregulation of Rho-associated coiled coil-containing protein kinases (ROCKs) is implicated in malignant tumor progression.
  • The specific role of ROCK1 in regulating glycolysis within tumor cells remains unclear.
  • This study investigates ROCK1's influence on pancreatic cancer (PC) progression through glycolytic activity.

Purpose of the Study:

  • To elucidate the mechanism by which ROCK1 regulates glycolytic activity in pancreatic cancer cells.
  • To determine the potential of targeting ROCK1 as a therapeutic strategy for pancreatic cancer.

Main Methods:

  • In vitro analysis using a ROCK1-silenced pancreatic cancer cell model.
  • Coimmunoprecipitation and luciferase reporter assays to investigate protein-protein interactions and gene promoter binding.
  • In vivo animal experiments to validate findings and assess therapeutic efficacy.

Main Results:

  • ROCK1 is highly expressed in PC tissues and associated with poor prognosis.
  • ROCK1 silencing inhibited PC cell proliferation and migration, promoting apoptosis.
  • ROCK1 directly interacts with c-MYC, stabilizing it and increasing PFKFB3 transcription, thereby enhancing glycolysis and promoting PC growth.
  • ROCK1 inhibition increased sensitivity to gemcitabine (GEM) in vitro and in vivo.

Conclusions:

  • ROCK1 promotes pancreatic cancer growth by enhancing glycolytic activity via the c-MYC/PFKFB3 signaling pathway.
  • ROCK1 knockdown inhibits tumor growth and increases gemcitabine sensitivity in pancreatic cancer.
  • Targeting ROCK1 represents a potential clinical therapeutic strategy for pancreatic cancer.

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