CX43/GJA1 Cancer Research Results

CX43/GJA1, Connexin 43 / Gap Junction Protein Alpha 1: Click to Expand ⟱
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Type:

CX43 - Connexin 43 / Gap Junction Protein Alpha 1

Abbreviation: CX43, GJA1

Type: Gap junction / hemichannel protein

Function: Major connexin protein that forms intercellular gap-junction channels and unopposed hemichannels. CX43 regulates direct cell-to-cell communication, ion and metabolite transfer, calcium signaling, proliferation, differentiation, migration, inflammatory signaling, and interactions between tumor cells and the surrounding stroma.

Cancer: ↕ Context-dependent. CX43 frequently acts as a tumor suppressor during early tumorigenesis by maintaining gap-junction intercellular communication and limiting proliferation. However, CX43 can become pro-tumorigenic during later disease stages by promoting migration, invasion, tumor-stromal communication, survival, and metastatic colonization. Direction therefore depends strongly on cancer type, disease stage, cellular localization, and whether gap-junction, hemichannel, or non-channel functions predominate.

Alzheimer's Disease: ↑ CX43 expression and hemichannel activity are increased in reactive astrocytes associated with amyloid plaques. Excessive CX43 hemichannel opening can promote ATP and glutamate release, abnormal Ca2+ signaling, neuroinflammation, and neuronal injury. CX43 hemichannel inhibition has shown neuroprotective effects in experimental amyloidosis models.
Scientific Papers found: Click to Expand⟱
7321- Gos,    The potential roles of gossypol as anticancer agent: advances and future directions
- Review, Var, NA
other↝, Except in China, where gossypol is available on the drug market as an adjuvant used for tumour treatment [85], in the rest of the world, gossypol is still under clinical trials investigation.
BioAv↑, To improve the water solubility and bioavailability of gossypol, Wang et al. [76] used gossypol-loaded pluronic F127 nanoparticles (GLPFNs), which increased bioavailability several times and exhibited higher organ uptake of the drug compared to using
Bcl-2↓, The main mechanism of gossypol-anticancer activity is inducing apoptosis through suppressing anti-apoptotic proteins of the Bcl-2 family.
Casp3↑, The caspase-dependent anti-tumour effect of gossypol is led by activation of caspase-3 and caspase-9.
Casp9↑,
MOMP↑, Apoptosis induced by independent pathways is made by alternations on the mitochondrial outer membrane permeabilisation
ROS↑, Gossypol treatment has been demonstrated to induce the production of reactive oxygen species (ROS) in tumour cell
ATP↓, 80 μmol/L gossypol resulted in a significant increase in cellular ROS levels, leading to ATP depletion, which induces mitochondrial dysfunction
mtDam↑,
Apoptosis↑, The impaired function of mitochondria further contributes to the activation of apoptosis
hTERT/TERT↓, ↓ decrease, telomerase reverse transcriptase (TERT)
Akt↓, ↓ decrease, telomerase reverse transcriptase (TERT), Adenosine triphosphate (ATP), Cellular myelocytomatosis oncogene (c-MyC), serine/threonine protein kinase (Akt)
TumAuto↑, Induction of autophagy as a complementary process of apoptosis
LC3‑Ⅱ/LC3‑Ⅰ↑, gossypol in colorectal cancer cells increased the LC3-II/LC3-I ratio and induced autophagy
NRF2↓, gossypol reduced Nrf2 protein stability, leading to the inhibition of the Nrf2/ARE pathway, resulting in a significant decrease of cell viability in human cancer cells
ARE↓,
ICAM-1↓, Treating breast cancer cells with gossypol has been shown to block the binding of NF-κB to the promoter regions of ICAM-1, suppressing TNF-α-induced ICAM-1 expression.
CX43/GJA1↓, It down-regulates the expression of CX43, nuclear NF-κB, TNF-α, toll-like receptor 4 (TLR4), and interleukin-6 (IL-6) in these cells, indicating its potential anti-inflammatory and anti-apoptotic effects
NF-kB↓,
TLR4↓,
IL6↓,
Inflam↓,
CUL5↝, gossypol has been found to block the neddylation of cullin enzymes (CUL5 and CUL1) by directly binding to the SAG-CUL5 or RBX1-CUL1 complex.
CUL1↝,
NOXA↑, This leads to the accumulation of both the pro-apoptotic protein NOXA
TumCI↓, gossypol significantly reduced the invasion, migration, and adhesion of these cancer cells by suppressing the FAK pathway and ETM
TumCMig↓,
TumCA↓,
FAK↓,
MDM2↓, gossypol, the binding between the MDM2 protein and VEGF mRNA was disrupted in breast cancer cells [78]. As a result, the expression of MDM2 and VEGF proteins is significantly decreased.
VEGF↓,
angioG↓, anti-angiogenic mechanism of gossypol in cancer cells (Fig. 7).
HLA-I/II↑, gossypol has been found to increase the expression of HLA-I/II molecules
Imm↑, This immune modulation may contribute to its anti-cancer activity by enhancing immune recognition and response against tumour cells
Dose↝, phase III clinical trial performed between January 2014 and February 2017, gossypol acetate tablets (20 mg/tablet) produced by Xi’an Northern Pharmaceutical Co., Ltd were tested with a placebo in 102 patients with NSCLC
Glycolysis↓, Moreover, the treatment of boars with gossypol inhibited glycolysis and the respiratory chain, leading to a decrease in oxidative phosphorylation and adenosine triphosphate (ATP) synthesis, causing a decrease in energy supply and inhibition of sperm
OXPHOS↓,


Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

CUL1↝, 1,   CUL5↝, 1,   CX43/GJA1↓, 1,   HLA-I/II↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

ARE↓, 1,   NRF2↓, 1,   OXPHOS↓, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,   mtDam↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

Glycolysis↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   Apoptosis↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   Casp9↑, 1,   hTERT/TERT↓, 1,   MDM2↓, 1,   MOMP↑, 1,   NOXA↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↝, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   TumAuto↑, 1,  

Migration(tgid=13) ⓘ

FAK↓, 1,   TumCA↓, 1,   TumCI↓, 1,   TumCMig↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

ICAM-1↓, 1,   IL6↓, 1,   Imm↑, 1,   Inflam↓, 1,   NF-kB↓, 1,   TLR4↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   Dose↝, 1,  

Clinical Biomarkers(tgid=22) ⓘ

hTERT/TERT↓, 1,   IL6↓, 1,  
Total Targets: 39

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: CX43/GJA1, Connexin 43 / Gap Junction Protein Alpha 1
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

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