Related Experiment Video

Updated: Jun 23, 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

PROK1 Induces Macrophage M2 Phenotype Conversion to Promote Pancreatic Cancer Progression by Activating the PI3K/AKT

Lan Ma1, Xiaogang Yan2, Di Liu3

  • 1Ningxia Medical University, Yinchuan, China.

Applied Biochemistry and Biotechnology
|June 22, 2026
PubMed

Insights

PROK1 promotes pancreatic cancer (PC) progression by converting macrophages to a pro-tumor M2 phenotype via the PI3K/AKT pathway. Targeting PROK1 may offer new therapeutic strategies for PC.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Pancreatic cancer (PC) progression is influenced by the tumor microenvironment, particularly macrophages.
  • The role of PROK1 and its receptor PROKR2 in PC and their interaction with macrophages requires further elucidation.

Purpose of the Study:

  • To investigate the impact and mechanisms of PROK1 on macrophage polarization and pancreatic cancer progression.
  • To explore the PROK1-PROKR2 interaction and its downstream signaling in PC.

Main Methods:

  • Immunohistochemistry and Western blot to detect PROK1/PROKR2 expression.
  • TIMER database analysis for macrophage infiltration correlation.
  • Immunofluorescence and Western blot for M2 phenotype markers and PI3K/AKT pathway activity.
  • Cell-based assays (CCK-8, wound healing, Transwell) and in vivo xenograft models.

Main Results:

  • PROK1/PROKR2 overexpression correlated with increased macrophage infiltration, advanced TNM stage, and metastasis in PC patients.
  • PROK1 silencing suppressed M2 polarization and PI3K/AKT pathway activation, reducing PC cell viability, migration, and invasion.
  • PROK1 interacted with PROKR2 to activate PI3K/AKT in macrophages, promoting M2 phenotype and PC growth in vivo.

Conclusions:

  • PROK1 drives pancreatic cancer progression by inducing M2 macrophage polarization through the PROK1-PROKR2-PI3K/AKT axis.
  • Targeting the PROK1 pathway in macrophages presents a potential therapeutic strategy for pancreatic cancer.
Keywords:
M2 macrophagesPCPI3K/AKTPROK1PROKR2

More Related Videos

Automated Imaging and Analysis for the Quantification of Fluorescently Labeled Macropinosomes11:01

Automated Imaging and Analysis for the Quantification of Fluorescently Labeled Macropinosomes

Published on: August 24, 2021

Related Concept Videos

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 rapamycin-insensitive companion...
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...
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 daughter...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...