KAT7 promotes radioresistance through upregulating PI3K/AKT signaling in breast cancer

Yan Ma1,2, Xiaohua Chen2, Ting Ding3

  • 1The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu, 730000, P. R. China.

Insights

Lysine acetyltransferase 7 (KAT7) promotes breast cancer radioresistance by upregulating PIK3CA and activating PI3K/AKT signaling. Targeting KAT7 may improve predicting and treating radioresistant breast cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Chromatin-modifying enzymes play crucial roles in cancer development, but their precise mechanisms are often unclear.
  • Lysine acetyltransferase 7 (KAT7) alterations are implicated in various cancers, necessitating further investigation into its role in breast cancer progression.

Purpose of the Study:

  • To elucidate the molecular mechanism by which KAT7 influences breast cancer radioresistance.
  • To evaluate KAT7 as a potential predictive biomarker and therapeutic target for radioresistant breast cancer.

Main Methods:

  • Quantitative analysis of KAT7 expression in breast cancer tissues.
  • In vitro experiments involving KAT7 silencing and overexpression in breast cancer cell lines.
  • Assessment of PIK3CA transcription, PI3K/AKT signaling pathway activation, and radioresistance levels.
  • Utilizing KAT7 acetyltransferase activity-deficient mutants to discern the role of enzymatic activity.

Main Results:

  • KAT7 expression was significantly upregulated in breast cancer and correlated with poorer patient survival.
  • KAT7 silencing markedly reduced breast cancer cell radioresistance in vitro.
  • KAT7 was found to activate Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) transcription, thereby enhancing PI3K/AKT signaling and promoting radioresistance.
  • Overexpression of AKT or PIK3CA rescued the radioresistance defect caused by KAT7 inhibition, confirming the pathway's importance.
  • KAT7's enzymatic activity, not just its presence, was crucial for promoting AKT phosphorylation, PIK3CA expression, and radioresistance.

Conclusions:

  • KAT7 plays a critical role in promoting breast cancer radioresistance through the PIK3CA/PI3K/AKT signaling pathway.
  • KAT7 represents a promising therapeutic target for overcoming radioresistance in breast cancer patients.
  • KAT7 expression levels may serve as a valuable biomarker for predicting radioresistance in breast cancer.

Related Concept Videos

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...
3.8K
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...
3.8K
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...
6.4K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K
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...
7.8K
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...
4.6K