Related Experiment Video

Updated: May 2, 2026

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

6.5K

Prolyl-isomerase Pin1 impairs trastuzumab sensitivity by up-regulating fatty acid synthase expression

Hyo Jeong Yun1, Jin Young Kim, Garam Kim

  • 1College of Pharmacy, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 501-759 Korea, chs@chosun.ac.kr.

Anticancer Research
|March 6, 2014
PubMed
Abstract

Insights

Fatty acid synthase (FAS) overexpression, regulated by Pin1, drives resistance to trastuzumab in HER2-positive breast cancer. Inhibiting Pin1 enhances trastuzumab efficacy, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Trastuzumab is an effective anti-HER2 monoclonal antibody for metastatic breast cancer.
  • Understanding resistance mechanisms to trastuzumab is crucial for improving patient outcomes.
  • Fatty acid synthase (FAS) expression is implicated in trastuzumab resistance in HER2-positive breast cancers.

Purpose of the Study:

  • To investigate the role of fatty acid synthase (FAS) in trastuzumab resistance.
  • To elucidate the mechanisms of FAS up-regulation in HER2-positive breast cancer.
  • To evaluate the potential of targeting FAS or its regulators to overcome trastuzumab resistance.

Main Methods:

  • Immunoblotting to assess protein expression.
  • BrdU incorporation and TUNEL assays to measure cell proliferation and apoptosis.
  • Soft agar assay to evaluate anchorage-independent growth.
  • Investigated the effects of trastuzumab in combination with juglone (a Pin1 inhibitor) and gene silencing of Pin1.

Main Results:

  • Pin1 enhances EGF-induced SREBP1c promoter activity, leading to increased FAS expression in BT474 cells.
  • Juglone, a Pin1 inhibitor, significantly enhanced trastuzumab-induced FAS down-regulation and cell death.
  • Combination therapy with trastuzumab and Pin1 inhibition (chemical or gene silencing) increased cleaved PARP and DNA fragmentation, enhancing trastuzumab sensitivity.

Conclusions:

  • Pin1-mediated overexpression of FAS is a key regulator of trastuzumab resistance in breast cancer.
  • Inhibiting Pin1 in combination with trastuzumab can overcome resistance and promote cancer cell death.
  • Targeting the Pin1-FAS pathway represents a promising strategy for treating trastuzumab-resistant HER2-positive breast cancer.
Keywords:
FASHER2Pin1Trastuzumabchemoresistance

More Related Videos

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

2.3K
Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity09:32

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity

Published on: October 17, 2025

661

Related Concept Videos

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...
4.0K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.0K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
81
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...
5.1K
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...
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...
3.6K