Related Experiment Video

Updated: Oct 12, 2025

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

3.2K

PLEKHA7 signaling is necessary for the growth of mutant KRAS driven colorectal cancer

Hei-Cheul Jeung1, Roisin Puentes2, Alexander Aleshin2

  • 1MD Anderson Cancer Center, Houston, TX, USA; Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Gangnam-Gu, Seoul, South Korea.

Experimental Cell Research
|November 20, 2021
PubMed

Insights

Plekha7 protein promotes colorectal cancer (CRC) growth by interacting with mutant KRas, enhancing its signaling. Inhibiting Plekha7 or its PH domain specifically hinders mutant KRas CRC progression.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Cancer Research

Background:

  • Plekha7 (Pleckstrin homology domain containing, family A member 7) is crucial for cell-cell adhesion and tight-junction integrity.
  • Plekha7 expression is elevated in colorectal cancer (CRC) and correlates with clinical stage.
  • The role of Plekha7 in cancer, particularly with KRas mutations, is largely unknown.

Purpose of the Study:

  • To investigate the function of Plekha7 in colorectal cancer (CRC) with wild-type (wt) and mutant (mut) KRas.
  • To elucidate the interaction between Plekha7 and KRas in CRC cells.
  • To determine the therapeutic potential of targeting Plekha7 in mut-KRas CRC.

Main Methods:

  • Utilized fluorescence lifetime imaging microscopy (FLIM) to assess Plekha7-KRas interactions.
  • Investigated the effect of Plekha7 inhibition on mut-KRas CRC cell signaling, proliferation, and migration.
  • Examined the role of the Plekha7 PH domain in binding phosphoinositides and its impact on mut-KRas CRC growth.

Main Results:

  • Plekha7 localized to the apical junction in wt-KRas cells but dispersed in mut-KRas cells.
  • Plekha7 directly interacted with wt-KRas but minimally with mut-KRas.
  • Inhibition of Plekha7 or its PH domain specifically impaired mut-KRas CRC cell signaling, proliferation, migration, and tumor growth, but not wt-KRas cells.

Conclusions:

  • Plekha7 plays a significant role in promoting mut-KRas CRC progression beyond its role in cell adhesion.
  • Plekha7 interacts with mut-KRas, enhancing downstream signaling and cellular phenotype.
  • Targeting Plekha7, particularly its PH domain, represents a promising therapeutic strategy for mut-KRas colorectal cancer.
Keywords:
Mutant KRASPH domainPLEKHA7

More Related Videos

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

14.0K
A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells10:13

A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells

Published on: July 3, 2013

11.3K

Related Concept Videos

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...
6.5K
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...
4.7K
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...
3.9K
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...
6.6K
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...
4.1K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.2K