PHLDA3

What is PHLDA3 Protein?

PHLDA3 is a type of protein that's starting to get attention in cancer research. It's known as a tumor suppressor because it can slow down or halt the growth of cancer cells. What makes PHLDA3 interesting is its role in the PI3K-Akt pathway, a key player in cell survival and growth. By competing with other molecules in this pathway, PHLDA3 keeps the Akt protein from being activated. This can slow down cancer progression, making it a potential target for therapies, especially in cancers like prostate and neuroendocrine tumors. Researchers are diving deeper into how PHLDA3 works, hoping to unlock new treatment options for tough-to-treat cancers.

What is the Function of PHLDA3 Protein?

PHLDA3 is like a traffic cop for cell growth, especially in controlling the PI3K-Akt pathway. This pathway often helps cancer cells thrive, so when PHLDA3 blocks Akt activation, it slows down the cancer cells. By limiting this growth pathway, PHLDA3 acts like a natural defense against tumors, potentially offering a new angle for cancer therapies. This is particularly important for aggressive cancers like prostate and pancreatic types, where researchers are looking into boosting PHLDA3 to stop tumor progression effectively.

PHLDA3 Related Signaling Pathway

PHLDA3 is important for keeping the PI3K-Akt signaling pathway in check, which is a crucial path that cells use to grow and survive. When this pathway goes into overdrive, it can lead to cancer. PHLDA3 jumps into action by getting in the way of molecules that activate Akt, a key protein in this process. It basically stops Akt from turning on, which helps slow down cell growth. This makes PHLDA3 a crucial player in preventing uncontrolled cell multiplication, especially in tough cancers like prostate and pancreatic. Figuring out how PHLDA3 works in this pathway could lead to new ways to treat cancer by targeting these specific processes.

PHLDA3 Related Diseases

PHLDA3 is tied to various diseases, mostly different types of cancer. It's supposed to help control how cells grow by keeping a check on the PI3K-Akt pathway. But when PHLDA3 levels drop, this pathway can run wild, leading to tumors, particularly in cancers like prostate and pancreatic cancer. Scientists see PHLDA3 as a promising target for cancer therapy because it can keep cell growth under control. Its link to these cancers makes it an important focus for developing new treatments to tackle these aggressive diseases.

Bioapplications of PHLDA3

PHLDA3 is gaining attention in biotechnology, especially for cancer research and therapies. It plays a big role in keeping cell growth in check by targeting the PI3K-Akt pathway. This makes it a potential game-changer for developing new cancer treatments, as scientists aim to use PHLDA3 to stop tumors from growing, particularly in tough cancers like prostate and pancreatic cancer. PHLDA3’s role in controlling cell signaling opens up possibilities for tackling other diseases with abnormal cell growth, making it a key focus for future medical breakthroughs.

Case Study 1: Ma S. et al. Biochem Biophys Res Commun. 2021

PHLDA3 is a protein linked to cancer, but its role in prostate cancer isn't well-understood. This research found that PHLDA3 levels are low in prostate cancer and associated with poor patient survival. Increasing PHLDA3 can slow cancer cell growth, arrest the cell cycle, and enhance sensitivity to docetaxel, a chemotherapy drug. It works by inhibiting the Akt pathway and Wnt/β-catenin signaling, reducing tumor growth in tests. These results suggest PHLDA3 could be a potential target for prostate cancer treatment.

• 
  Fig1. Expression levels of PHLDA3 in prostate cancer cell lines were examined via western blot.
• 
  Fig2. The effects of PHLDA3 overexpression on the levels of c-myc and cyclin D1 were assessed via western blotting.

Case Study 2: Takikawa M. et al. Cancer Sci. 2017

Pancreatic neuroendocrine tumors (PanNET) are rare and tough to treat. Understanding their development is key for better diagnosis and treatment. The mTOR inhibitor everolimus can help patients by blocking the PI3K-Akt-mTOR pathway, which plays a role in PanNET progression. Here the tumor suppressor PHLDA3, which inhibits Akt, is often suppressed in PanNET due to genetic changes. Similar issues with PHLDA3 are seen in lung neuroendocrine tumors, indicating a common trend across different NET types.

• 
  Fig3. Binding of GST-PHLDA3, GST-PH-Akt or GST to immobilized PIP was assessed by protein-lipid overlay assay.
• 
  Fig4. Effect of PHLDA3 expression on Akt activity in MIN6 cells.

• 
  Fig1. A proposed graphical model for the PHLDA3-mediated Akt/Wnt/β-catenin pathway in prostate cancer progression. (Shuaijun Ma, 2021)
• 
  Fig2. A model of Akt repression by PHLDA3. (Yu Chen, 2020)

PHLDA3 has several biochemical functions, for example, phosphatidylinositol-3,4,5-trisphosphate binding,phosphatidylinositol-3,4-bisphosphate binding,phosphatidylinositol-3,5-bisphosphate binding. Some of the functions are cooperated with other proteins, some of the functions could acted by PHLDA3 itself. We selected most functions PHLDA3 had, and list some proteins which have the same functions with PHLDA3. You can find most of the proteins on our site.

Function	Related Protein
phosphatidylinositol-3,4,5-trisphosphate binding	D6WSU116E,KIF16B,GAB2,ARAP2,PIRT,ARHGAP9,ZFYVE1,JPH2,AKT1,ARAP1
phosphatidylinositol-4,5-bisphosphate binding	TWF1,Apba1,KCNJ1,FAM21C,TIRAP,CHMP3,EXOC1,FCHO2,ADAP2,KRIT1
phosphatidylinositol-3,4-bisphosphate binding	MYO1G,COMMD1,ZFYVE1,GAB2,SESTD1,MAPKAP1,RS1,AKT1,ADAP2,ANXA8
phosphatidylinositol-5-phosphate binding	SH3PXD2B,PLEKHF1,SESTD1,RS1,SNX3,FAM21C,LANCL2,JPH2,SNX24,D6WSU116E
phosphatidylinositol-3,5-bisphosphate binding	GBF1,FAM21C,SNX14,SNX3,SH3PXD2B,WDR45,MAPKAP1,WDR45B,CLVS2,COMMD1
phosphatidylinositol-3-phosphate binding	NCF4,WDR45,BBS5,KIF16B,WIPI1,ZFYVE19,LANCL2,WIPI2,WDR45B,D6WSU116E

PHLDA3 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with PHLDA3 here. Most of them are supplied by our site. Hope this information will be useful for your research of PHLDA3.

MYO1C;RFXANK;POLR1C;ZW10;IDH3B;DPM1;DNAJB6;SLC25A12;TRIO;ATP5L;MYO1D;UFL1;PRPF6;AHSA1;NTRK1;RPN2