Downregulation of SSR2 Enhances Hepatocellular Carcinoma Cisplatin Sensitivity via the Hippo Pathway

Rong Ye1, Ling Yin2, Yilong Ge3

  • 1Department of General Surgery III, The First Affiliated Hospital of Gannan Medical University, 341000 Ganzhou, Jiangxi, China.

Abstract

Insights

Signal sequence receptor subunit 2 (SSR2) upregulation promotes hepatocellular carcinoma (HCC) progression and chemoresistance. Targeting the SSR2/Hippo axis may enhance chemotherapy effectiveness in HCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Hepatocellular carcinoma (HCC) chemoresistance limits patient survival.
  • Novel therapeutic targets are needed to overcome HCC chemotherapy resistance.

Purpose of the Study:

  • To investigate the role of Signal sequence receptor subunit 2 (SSR2) in HCC.
  • To explore SSR2 as a potential therapeutic target for enhancing HCC chemotherapy.

Main Methods:

  • Quantitative real-time polymerase chain reaction (qPCR) and Western blotting for SSR2 expression.
  • Assays for cell proliferation, apoptosis, and anchorage-independent growth.
  • In vivo animal models and molecular mechanism studies (luciferase reporter assays).

Main Results:

  • SSR2 is upregulated in HCC and linked to poor patient survival.
  • Downregulation of SSR2 increases HCC sensitivity to Cisplatin (DDP).
  • SSR2 inhibits YAP phosphorylation, promoting Hippo pathway gene transcription.

Conclusions:

  • SSR2 plays a critical role in HCC progression through the Hippo pathway.
  • Targeting the SSR2/Hippo axis is a potential strategy to overcome DDP resistance in HCC.

Related Concept Videos

Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.1K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K
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...
3.4K
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...
6.2K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.0K
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...
4.5K