Related Experiment Video

Updated: Apr 26, 2026

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

5.7K

SHP-1 is a target of regorafenib in colorectal cancer

Li-Ching Fan1, Hao-Wei Teng2, Chung-Wai Shiau3

  • 1Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei, Taiwan; These authors contributed equally to this work.

Oncotarget
|July 30, 2014
PubMed

Insights

Regorafenib enhances SHP-1 activity, reducing p-STAT3 in colorectal cancer. This mechanism promotes apoptosis and tumor suppression, offering a new therapeutic strategy for CRC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Metastatic colorectal cancer (CRC) remains a significant health challenge.
  • Regorafenib shows antitumor and antimetastatic effects in CRC by inhibiting protein kinases.
  • SHP-1 phosphatase activity is linked to tumor suppression via negative regulation of p-STAT3 signaling.

Purpose of the Study:

  • To elucidate the mechanism by which regorafenib enhances SHP-1 activity in CRC.
  • To investigate the role of SHP-1 modulation in regorafenib-induced apoptosis and tumor suppression.
  • To determine if regorafenib acts as a direct SHP-1 agonist.

Main Methods:

  • In vitro assays to assess SHP-1 activity and its interaction with regorafenib.
  • Analysis of p-STAT3(Tyr705) levels following regorafenib treatment.
  • Genetic manipulation of SHP-1 (N-SH2 domain deletion, D61A mutation) to study its role.
  • In vivo xenograft models to evaluate regorafenib's anti-tumor efficacy.

Main Results:

  • Regorafenib treatment induced significant apoptotic cell death and enhanced SHP-1 activity in CRC cells.
  • Enhanced SHP-1 activity led to a marked decrease in p-STAT3(Tyr705) levels.
  • Regorafenib disrupted the autoinhibitory interaction within SHP-1, increasing its catalytic activity.
  • SHP-1 mutations abrogated regorafenib's effects on SHP-1 activity, p-STAT3, and cell growth.
  • In vivo studies confirmed regorafenib's inhibition of tumor growth and decreased p-STAT3(Tyr705) with increased SHP-1 activity.

Conclusions:

  • Regorafenib functions as a novel SHP-1 agonist, enhancing its activity to suppress tumor growth.
  • The mechanism involves regorafenib-induced conformational changes in SHP-1, relieving autoinhibition.
  • Targeting p-STAT3(Tyr705) through enhanced SHP-1 activity represents a promising therapeutic strategy for CRC.
  • Small molecule-mediated enhancement of SHP-1 activity holds potential for CRC treatment.

More Related Videos

Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer08:12

Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer

Published on: March 14, 2019

5.1K
Portal Vein Injection of Colorectal Cancer Organoids to Study the Liver Metastasis Stroma07:59

Portal Vein Injection of Colorectal Cancer Organoids to Study the Liver Metastasis Stroma

Published on: September 3, 2021

6.0K

Related Concept Videos

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
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

1.4K
Treatment Resistent Cancers02:56

Treatment Resistent Cancers

1.1K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
2.6K
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
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.5K