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TUBB4A interacts with MYH9 to protect the nucleus during cell migration and promotes prostate cancer via

Song Gao1, Shuaibin Wang1, Zhiying Zhao1

  • 1Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.

Nature Communications
|May 19, 2022
PubMed

Insights

High expression of human tubulin beta class IVa (TUBB4A) in prostate cancer correlates with aggressive disease and poor survival. TUBB4A’s oncogenic role suggests it as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Human tubulin beta class IVa (TUBB4A) is a β-tubulin protein.
  • TUBB4A is minimally expressed in normal tissues but highly expressed in prostate cancer.
  • High TUBB4A expression is linked to aggressive prostate cancer and reduced patient survival, particularly in African-American men.

Purpose of the Study:

  • To investigate the oncogenic role of TUBB4A in prostate cancer.
  • To explore the mechanisms by which TUBB4A influences prostate cancer progression.
  • To identify TUBB4A as a potential therapeutic target.

Main Methods:

  • TUBB4A knockout (KO) in prostate cancer cells.
  • Analysis of cell growth, migration, and DNA damage markers (γH2AX, 53BP1).
  • Investigation of TUBB4A interactions with MYH9 during cell migration.
  • Assessment of signaling pathways including NF-κB, β-catenin, and epithelial-mesenchymal transition (EMT).
  • Prostate-specific deletion of Tubb4a in a mouse model.

Main Results:

  • TUBB4A KO reduced prostate cancer cell growth and migration while increasing DNA damage.
  • TUBB4A interacts with MYH9 to protect the nucleus during constricted migration, preventing DNA damage and maintaining NF-κB signaling.
  • TUBB4A KO and MYH9 knockdown led to severe DNA damage and reduced NF-κB response.
  • TUBB4A KO inhibited tumor growth and metastasis.
  • TUBB4A/GSK3β binding to MYH9 regulates GSK3β ubiquitination and degradation, impacting β-catenin signaling and EMT.
  • Prostate-specific Tubb4a deletion suppressed tumor growth and metastasis by inhibiting NF-κB, cyclin D1, and c-MYC signaling.

Conclusions:

  • TUBB4A plays a significant oncogenic role in prostate cancer.
  • TUBB4A promotes prostate cancer progression and metastasis through interactions with MYH9 and regulation of key signaling pathways.
  • TUBB4A represents a promising therapeutic target for prostate cancers with TUBB4A overexpression.

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