ASAP1 promotes extrahepatic cholangiocarcinoma progression by regulating the Wnt/β-catenin pathway in vitro and in vivo

  • 0Department of General Surgery, Zhongshan Hospital Affiliated to Fudan University Shanghai 200032, China.

|

|

Summary

This summary is machine-generated.

ADP-ribosylation factor GTPase-activating protein (ASAP1) promotes extrahepatic cholangiocarcinoma (EHCC) development by enhancing cell proliferation and Wnt/β-catenin pathway activity. ASAP1 inhibition offers a potential therapeutic strategy for EHCC.

Area Of Science

  • Oncology
  • Molecular Biology
  • Biochemistry

Background

  • Extrahepatic cholangiocarcinoma (EHCC) is an aggressive biliary tract cancer with limited therapeutic options.
  • Understanding the molecular drivers of EHCC progression is crucial for developing targeted therapies.
  • ADP-ribosylation factor GTPase-activating protein (ASAP1) has been implicated in various cancers, but its role in EHCC is not well-defined.

Purpose Of The Study

  • To investigate the expression of ASAP1 in EHCC.
  • To determine the relationship between ASAP1 expression and clinical outcomes in EHCC patients.
  • To elucidate the functional role of ASAP1 in EHCC cell proliferation, migration, invasion, and tumor development.

Main Methods

  • ASAP1 expression was analyzed using quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry in EHCC tissues and cell lines.
  • Cell proliferation was assessed via Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays.
  • Cell cycle distribution and apoptosis were analyzed by flow cytometry. In vitro and in vivo experiments evaluated ASAP1's role in tumor development.

Main Results

  • ASAP1 expression was significantly correlated with clinical outcomes in EHCC patients.
  • ASAP1 knockdown inhibited cell proliferation, cell cycle progression, and induced apoptosis in EHCC cells.
  • ASAP1 promoted EHCC cell migration and invasion by regulating Wnt/β-catenin pathway activity and facilitated tumor development in vivo.

Conclusions

  • ASAP1 plays a critical role in the tumorigenesis and progression of extrahepatic cholangiocarcinoma.
  • ASAP1 enhances EHCC cell proliferation, migration, invasion, and tumor development.
  • ASAP1 represents a promising therapeutic target for the treatment of EHCC.

Related Concept Videos

Canonical Wnt Signaling Pathway 02:54

8.7K

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...

mTOR Signaling and Cancer Progression 03:03

3.7K

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 Proliferation 02:23

4.4K

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...

Tumor Progression 02:07

6.2K

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...

Non-Canonical Wnt Signaling Pathways 01:41

7.2K

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...

The Intrinsic Apoptotic Pathway 01:31

6.4K

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...