LATS2 induced by TNF-alpha and inhibited cell proliferation and invasion by phosphorylating YAP in oral squamous cell

Cong Dong1,2, Kui-Jie Wei3, Wen-Bin Zhang1

  • 1Shanghai Key Laboratory of Stomatology, Department of Oral and Cranio-Maxillofacial Science, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Insights

Large tumor suppressor 2 (LATS2) inhibits oral squamous cell carcinoma (OSCC) progression by phosphorylating YAP. Tumor necrosis factor-alpha (TNF-α) induces LATS2, suggesting LATS2 as a potential therapeutic target for OSCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Large tumor suppressor 2 (LATS2) is a known Hippo pathway component that phosphorylates and inactivates YAP, acting as a tumor suppressor in various human cancers.
  • The specific role and regulatory mechanisms of LATS2 in oral squamous cell carcinoma (OSCC) remain underexplored.

Purpose of the Study:

  • To investigate the role of LATS2 in OSCC.
  • To elucidate the mechanisms regulating LATS2 expression in OSCC.
  • To determine the functional impact of LATS2 on OSCC cell behavior.

Main Methods:

  • Western blotting to detect LATS2 and phosphorylated YAP expression in HN6 cells treated with TNF-α.
  • Luciferase reporter assays to confirm YAP phosphorylation by LATS2.
  • Assays for cell proliferation, anchorage-independent growth, invasion, and in vivo xenograft growth to assess the effects of LATS2 overexpression.

Main Results:

  • LATS2 was confirmed to phosphorylate YAP.
  • TNF-α dose- and time-dependently induced LATS2 expression in HN6 cells.
  • Overexpression of LATS2 significantly inhibited OSCC cell proliferation, colony formation, invasion, and in vivo tumor growth.

Conclusions:

  • LATS2, induced by TNF-α, inhibits OSCC cell proliferation and invasion via YAP phosphorylation.
  • LATS2 plays a critical role in OSCC tumorigenesis.
  • LATS2 represents a potential therapeutic target for OSCC treatment.

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
11.1K
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...
6.5K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
14.2K
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...
5.1K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

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...
9.3K
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...
5.5K